EIF2B1
TRUNCATED 302 aa (canonical 305 aa) · UniProt Q14232 · CDLMPS
chr12:123633548:-:AAG:ENST00000424014.7
AI summary A 4-residue N-terminal clip removes only the first two turns of a longer helix, with no domain, localization, or biophysical change detected.
How it diverges
The truncation deletes canonical residues Met1-Lys4, which fall within a 14-aa helix (residues 3-16), but the vast majority of that helix (12 of 14 residues) and its packing contacts against the core are retained in the shared sequence, and the shared-region fold is essentially unchanged (Cα RMSD 0.32 Å, TM-score 0.998, high pTM/pLDDT). No InterPro domain, DeepLoc compartment, targeting signal, whole-protein biophysical descriptor, or high-magnitude SAE feature shift is detected in association with this loss.
Why it matters
EIF2B1 encodes eIF2Bα, the regulatory subunit that docks phospho-eIF2α and confers stress-responsive translational control within the decameric eIF2B holoenzyme; this function depends on its cytosolic localization, its N-terminal eIF2Bα domain fold, and its surface for phospho-eIF2α/eIF2Bδ interaction. Because the removed 4 residues are only the very start of a helix whose bulk and structural integration are preserved, and because no mechanism-tier finding (domain, localization, fold, biophysics) shows a meaningful change, this truncation does not present clear evidence of disrupting the eIF2Bα docking surface, decamer assembly, or catalytic sugar-phosphate pocket described in the literature.
LLM confidence low
No mass-spec peptide validation of this isoform-unique region exists, and the affected helix's N-terminal two residues could plausibly matter for docking/complex assembly even though no computational finding captures this; absence of tier-2 signal does not rule out a real but undetected effect.
Folding
Canonical (305 aa)
Download CIF
Isoform (302 aa)
Download CIF
Coloured by ESMFold2 pLDDT confidence (blue = high, orange/red = low).
Differential region — residues 1–4 (lost from canonical) — recoloured on a yellow→purple pLDDT ramp so it stands out.
Drag to rotate · scroll to zoom · download a CIF to explore in your own viewer.
Canonical PAE
Isoform PAE
Predicted aligned error: expected Cα error (Å) at residue j when the fold is superposed on residue i. Dark = confident relative placement; bright = uncertain.
The dashed outline marks the differential region (1–4).
Evidence — click any tile for the differential-region detail
C
Conservation
Interesting
LLM reasoning
The N-terminal MDDK segment removed by this truncation is itself under strong purifying selection, arguing the truncation deletes functionally important canonical sequence rather than dispensable flexible tail. Mean phyloP over the unique region is 4.18 (vs 3.61 shared, strong constraint by the ~2 threshold), and amino-acid identity is high in both primates (94.7%) and mammals (85.0%), though both trail the canonical-region baselines (98.8% primate, 96.0% mammalian) — consistent with a real but somewhat less constrained coding segment relative to the rest of the protein. All three signals concur in direction, so despite being modestly below the whole-canonical-ORF conservation level, the removed region is clearly evolutionarily constrained coding sequence, making its loss in this truncation biologically consequential.
Unique region 94.7% similar across primates
How well is the isoform-unique region conserved at the amino-acid level across primates (mean percent identity)? High AA identity in close relatives argues the alternative protein is real and translated, not a sequencing or annotation artifact. (Reading-frame intactness is shown as context.)
Comparison
Sequence conservation · primate
mean AA identity over the differential ORF is the score basis; frame intactness across the clade is context
| Conservation metric | Canonical ORF | Differential ORF |
|---|---|---|
| Mean AA identity | 99% | 95% |
| Frame intact (fraction of species) | 96% | 100% |
| Species aligned | 25 | 25 |
| Species frame-intact | 24 | 25 |
| Start codon conserved | 100% | 100% |
| Deepest intact species | Microcebus_murinus | Microcebus_murinus |
| Phylo depth (MRCA) | 7 | 7 |
Unique region 85.0% similar across mammals
The same amino-acid identity test across mammals. Conservation over deeper evolutionary distance is stronger evidence the ORF is under selection to be translated. (Reading-frame intactness is shown as context.)
Comparison
Sequence conservation · mammalian
mean AA identity over the differential ORF is the score basis; frame intactness across the clade is context
| Conservation metric | Canonical ORF | Differential ORF |
|---|---|---|
| Mean AA identity | 96% | 85% |
| Frame intact (fraction of species) | 80% | 100% |
| Species aligned | 20 | 20 |
| Species frame-intact | 16 | 20 |
| Start codon conserved | 100% | 100% |
| Deepest intact species | Loxodonta_africana | Loxodonta_africana |
| Phylo depth (MRCA) | 12 | 12 |
Unique region PhyloP: 4.18 — purifying selection
phyloP / phastCons measure per-base evolutionary constraint. A high absolute phyloP over the differential region means the sequence itself is under strong purifying selection — evidence it is coding and does something. (Enrichment over the shared core is shown as context only.)
Comparison
Per-base conservation · differential region
absolute mean phyloP over the differential region is the score basis (high = strong purifying selection); the shared column and enrichment are context, not the claim
| Track | Differential | Shared | vs shared |
|---|---|---|---|
| phyloP mean | 4.18 | 3.61 | 1.16 |
| phastCons mean | 0.617 | 0.829 | — |
Start site · canonical vs isoform
initiation context + per-base conservation at each start codon
| Property | Canonical | Isoform |
|---|---|---|
| Start codon | ATG | AAG |
| Kozak context (−9..+4) | GAGGACGCCATGG | ATGGACGACAAGG |
| phyloP at start codon | 6.94 | -0.512 |
| phastCons at start codon | 1 | 0.001 |
| phyloP over Kozak window | 2.68 | 3.43 |
| phastCons over Kozak window | 0.761 | 0.458 |
| Kozak mismatch — full consensus | 3 | 6 |
| Kozak window GC content | 0.692 | 0.538 |
D
Detection
Neutral
LLM reasoning
This alt TIS has clear ribosome-profiling support in one cell line but no proteomic confirmation and no cross-line reproducibility. Start-site usage is real and statistically strong (HeLa initiation efficiency 0.103, Fisher q=1.2e-10), exceeding the canonical TIS efficiencies seen in other lines (0.016-0.155), but it was only tested/detected in 1 of 6 cell lines, with the rest lacking data rather than showing non-detection. Mass spec found zero validated unique peptides out of 2 candidate isoform-unique peptides, so there is no direct protein-level confirmation of the truncated N-terminus. Combined, this is solid but singular translational evidence with no independent peptide-level corroboration, landing as a mixed, unremarkable signal for this category.
detected in 1/6 cell lines
Is the alternative start used in more than one cell line? Reproducible initiation across independent samples argues against a one-off ribosome artifact.
Comparison
Per-cell-line usage · canonical vs isoform
Fisher q = 1.22e-10
| Cell line | Canonical | Isoform | p-value |
|---|---|---|---|
| HeLa | — | 9.66 | 1.22e-10 |
| K562 | 22.6 | — | — |
| U2OS | 2.21 | — | — |
| RPE1 Async | 1.09 | — | — |
| RPE1 Que | 0.676 | — | — |
Max Initiation Efficiency: 0.103
How efficiently ribosomes initiate at this start (TIS) relative to background, per cell line. Strong, reproducible initiation supports a genuine translation event.
Comparison
Start-Site Usage · canonical vs isoform
ribosome initiation efficiency at the canonical start vs this alternative start, per cell line
| Cell line | Canonical | Isoform |
|---|---|---|
| HeLa | — | 0.103 |
| K562 | 0.155 | — |
| U2OS | 0.0239 | — |
| RPE1 Async | 0.0194 | — |
| RPE1 Que | 0.0189 | — |
0/2 isoform-unique peptides validated
Were tryptic peptides unique to the differential region detected by mass spec? Direct peptide evidence is the strongest proof the isoform protein exists.
Comparison
Peptide Evidence (canonical vs isoform)
isoform-unique peptides are direct evidence the alternative protein exists
| Feature | Canonical | Isoform |
|---|---|---|
| Tryptic peptides (in-silico) | 40 | 2 |
| Validated by mass-spec | 0 | 0 |
| Isoform-unique peptides | — | 2 |
Details
Peptide Evidence (canonical vs isoform)
- peptide MELIEYFK 0–8
- peptide MELIEYFKSQMK 0–12
L
Localization
Not interesting
LLM reasoning
Loss of this short 4-residue N-terminal segment (MDDK) has no detectable effect on predicted localization: DeepLoc calls both isoform and canonical Cytoplasm/Nucleus with essentially identical top probabilities (0.707 vs 0.705), and the same nuclear localization/export signal annotations and soluble membrane status are retained in both. Sorting-signal predictions are likewise unchanged, with both canonical and isoform scored as no signal peptide (SignalP: OTHER) and no transit peptide (TargetP: noTP), and probability deltas near zero. The truncated region does not overlap any sorting or membrane-targeting determinant detected by these tools, arguing against a localization-relevant consequence of this truncation.
iso: Cytoplasm, Nucleus | canon: Cytoplasm, Nucleus
Do the predicted localization features (DeepLoc prediction, sorting signals, or membrane association) differ between the canonical and the isoform? A protein with changed localization features acts in a different cellular context.
Comparison
Subcellular localization (DeepLoc)
no localization-feature change
| Property | Canonical | Isoform |
|---|---|---|
| Predicted location | Cytoplasm|Nucleus | Cytoplasm|Nucleus |
| Sorting signals | Nuclear localization signal|Nuclear export signal | Nuclear localization signal|Nuclear export signal |
| Membrane | Soluble | Soluble |
iso: noTP | canon: noTP
Do N-terminal targeting signals (SignalP secretion, TargetP mitochondrial/chloroplast) differ between canonical and isoform? N-terminal changes most directly add or remove targeting peptides.
M
Mutation Landscape
Not interesting
LLM reasoning
The removed region is only 4 residues (canonical Met1-Lys4), carrying just 8 total variant records — 7 gnomAD (all rare, allele frequencies ~1e-5 to 1e-7) and a single ClinVar VUS, with zero pathogenic calls and zero COSMIC hits. Disease-variant density is depleted rather than enriched in this segment (enrichment ratio 0.36; 0 pathogenic vs 33 in the shared core), and the scored missense variants here are AlphaMissense likely_benign (mean 0.148, max 0.216) with the damaging flag false for all 8 rows. One gnomAD variant sits exactly at the canonical start codon (p.Met1?) but it is not annotated as start_lost, is not clinically flagged, and is population-observed at trace frequency — not a documented start-disruption event. The gnomAD depletion ratio (1.52) and ESM-C enrichment (1.81, but 0 constrained positions in the unique region) are both derived from a handful of variants over a 9-nt window and do not indicate real constraint. Overall this is a quiet 4-residue N-terminal truncation with no disease signal and no credible damaging variant burden.
gnomAD variants 1.52× more in unique region — tolerant
Does healthy human germline variation (gnomAD) avoid this region (depletion ratio < 1×), and is it intrinsically constrained (ESM-C constraint delta > 0)? Depletion of population variation plus high sequence constraint mean the region resists change — it is functionally important. Scored only where the unique region is canonical coding sequence, i.e. on truncations. gnomAD is a tolerance catalogue, not a disease one; disease/cancer variants (ClinVar / COSMIC) live in M2.
Comparison
Germline Variants · differential vs shared region
gnomAD (population) variant density per nucleotide — depletion ratio < 1× means healthy human variation avoids the region (constrained), the M1 basis alongside ESM-C constraint
| Variant set | Differential | Shared | Depletion ratio |
|---|---|---|---|
| gnomAD variants | 7 | 465 | 1.5× |
Sequence constraint (ESM-C) · differential vs shared region
lower LLR = more constrained; enrichment = differential / conserved
| Property | Differential | Shared | Enrichment |
|---|---|---|---|
| ESM-C mean LLR | -0.724 | -0.401 | — |
| Constrained positions | 0 | 3 | — |
Predicted-damaging variants · germline (gnomAD)
AlphaMissense / ESM-C / LoF calls per region (length-normalized)
| Variant set | Differential | Shared | Enrichment |
|---|---|---|---|
| Scorable variants | 7 | 459 | 1.2× |
| Damaging variants | 0 | 153 | 0× |
| — of which loss-of-function | 0 | 44 | 0× |
| AlphaMissense-pathogenic | 0 | 104 | 0× |
Predictor scores · germline (gnomAD)
scored: 673 ESM-C · 411 AlphaMissense
| Property | Differential | Shared |
|---|---|---|
| Mean ΔLLR (ESM-C) | -3.52 | -3.6 |
| Min ΔLLR (ESM-C) | -6.96 | -12.3 |
| Mean AlphaMissense | 0.141 | 0.463 |
Disease variants 2.80× less in unique region — depleted
Are disease (ClinVar / COSMIC) variants enriched per nucleotide in the differential region versus the shared core (disease enrichment ratio ≥ 1×)? Disease variants concentrating in the unique region tie it to phenotype.
Comparison
Clinical-variant burden · differential vs shared region
counts per region; ratio is density-normalized (variants per nucleotide, differential ÷ shared — ≥1× = disease variants concentrate in the differential region, the M2 basis)
| Variant set | Differential | Shared | Enrichment |
|---|---|---|---|
| Disease variants | 1 | 282 | 0.36× |
| Pathogenic | 0 | 33 | 0× |
Predicted-damaging variants · disease (ClinVar/COSMIC)
AlphaMissense / ESM-C / LoF calls per region (length-normalized)
| Variant set | Differential | Shared | Enrichment |
|---|---|---|---|
| Scorable variants | 1 | 278 | 0.27× |
| Damaging variants | 0 | 84 | 0× |
| — of which loss-of-function | 0 | 28 | 0× |
| AlphaMissense-pathogenic | 0 | 53 | 0× |
Predictor scores · disease (ClinVar/COSMIC)
scored: 673 ESM-C · 411 AlphaMissense
| Property | Differential | Shared |
|---|---|---|
| Mean ΔLLR (ESM-C) | -5.67 | -3.21 |
| Min ΔLLR (ESM-C) | -5.67 | -12.2 |
| Mean AlphaMissense | 0.179 | 0.47 |
P
Predicted Structure
Not interesting
LLM reasoning
The truncation removes only canonical residues 1-4 ("MDDK"), but the "lost" helix reported by the secondary-structure member spans canonical 3-16 (14 aa, pLDDT 0.97) — meaning just the first 2 residues of this helix fall inside the actual differential region, while residues 5-16 remain in the shared, retained sequence. This helix is confidently folded and well-integrated (mean PAE to the rest of the protein 2.19 Å over residues 3-16 vs. 17-305, with 35 contacts distributed across residues 18-59), but that integration is a property of the retained core, not something lost by this isoform. The shared-region Cα RMSD is negligible (0.32 Å, TM-score 0.998, min shared pLDDT 0.94, global pTM 0.95-0.96), confirming the retained portion of the helix and the rest of the fold are essentially unperturbed. Net effect: a 4-residue N-terminal clip that nicks the cap of a helix rather than eliminating a discrete structural element, so this does not read as a meaningful structural consequence.
pLDDT Differential Region:
0.973
Does the gained/lost region fold into ordered structure (pLDDT) and shift the protein's biophysical character (charge, hydropathy, disorder)? Structured, biophysically distinct regions are more likely to be functional.
Comparison
Structure (ESMFold2) · canonical vs isoform
TM-score 0.991 · RMSD 0.473 Å
| Metric | Canonical | Isoform |
|---|---|---|
| pLDDT (whole protein) | 0.943 | 0.939 |
Fold confidence · differential vs shared region
mean ESMFold2 pLDDT in each region
| Metric | Differential | Shared | Enrichment |
|---|---|---|---|
| pLDDT | 0.973 | 0.976 | 1 |
Shared-Region RMSD:
0.32 Å
The shared region is the stretch of protein identical in both the isoform and the canonical (the canonical body for an extension; the post-truncation body for a truncation). Folded in both contexts it normally comes out nearly identical, so its Cα backbone RMSD ≈ 0. A high shared-region RMSD (superposed on the shared residues only, from the ESMFold2 structures) means the extension or truncation reorganizes how the retained region folds — a rare, high-interest functional signal. TM-score is a length-normalized companion; the check only fires when both structures are confidently folded, and uORF/altORF isoforms (no shared region) are not evaluable.
Comparison
Shared-region structural change
Cα RMSD superposed on the shared residues only; TM-score is length-normalized · shared-region Cα RMSD 0.321 Å · shared TM-score 0.998 · shared region 301 aa · min shared pLDDT 0.94 · global TM-score 0.991 · global RMSD 0.473 Å
| Property | Canonical | Isoform |
|---|---|---|
| Shared-region pLDDT | 0.943 | 0.94 |
1 secondary structure identified in unique region
Does the differential region contain actual secondary structure — a helix or strand — rather than coil? ESMFold2 predicts coordinates but no secondary structure, so elements are assigned from those coordinates (P-SEA, Cα geometry). Because they are derived from a prediction, each element carries its own mean pLDDT: a geometrically clean helix running through a disordered stretch is geometry fitted to a guess, so BOTH length and confidence are required to score. The direction differs by ORF type — an extension GAINS the element (a candidate functional addition), a truncation LOSES one, and there the element is read off the canonical structure because the removed segment exists only in it. This says nothing about whether the element is integrated with the rest of the fold; the contact and PAE evidence in this same category answers that.
Comparison
Secondary structure · differential vs shared region
helices and strands assigned from the predicted coordinates (P-SEA)
| Metric | Differential | Shared |
|---|---|---|
| Alpha helices | 1 | 8 |
| Beta strands | 0 | 2 |
| Longest element (aa) | 14 | 29 |
| Mean pLDDT | 0.97 | 0.97 |
Elements and coordinates
1 in the differential region, 10 in the shared core — residue numbering is 1-based on the protein holding the region
| Removed (canonical) | Shared core |
|---|---|
| alpha helix 3–16 14 aa · pLDDT 0.97 | alpha helix 22–36 15 aa · pLDDT 0.97 |
| — | alpha helix 42–59 18 aa · pLDDT 0.96 |
| — | alpha helix 63–77 15 aa · pLDDT 0.93 |
| — | alpha helix 86–114 29 aa · pLDDT 0.95 |
| — | beta strand 122–127 6 aa · pLDDT 0.99 |
| — | alpha helix 132–144 13 aa · pLDDT 0.98 |
| — | alpha helix 160–171 12 aa · pLDDT 0.98 |
| — | alpha helix 211–222 12 aa · pLDDT 0.98 |
| — | beta strand 223–230 8 aa · pLDDT 0.99 |
| — | alpha helix 295–304 10 aa · pLDDT 0.95 |
Below threshold
0 in the differential region, 5 in the shared core — shorter than 6 aa or below pLDDT 0.70, so not counted above
| Removed (canonical) | Shared core |
|---|---|
| — | beta strand 148–152 5 aa · pLDDT 0.98 |
| — | beta strand 174–178 5 aa · pLDDT 0.98 |
| — | beta strand 205–207 3 aa · pLDDT 0.99 |
| — | beta strand 273–276 4 aa · pLDDT 0.98 |
| — | beta strand 283–285 3 aa · pLDDT 0.99 |
S
Structural Characteristics
Not interesting
LLM reasoning
None of the structural-characteristics submodules support a meaningful consequence of removing this 4-residue N-terminal segment (MDDK) from the canonical eIF2B1 protein. No real InterPro domain overlaps the differential region despite the isoform retaining an intact eIF2B alpha N-terminal domain hit. Whole-protein hydropathy, charge, and disorder deltas are all negligible (gravy delta 0.037, fraction-charged delta -0.007, disorder delta -0.003), well below any shift threshold, and this is expected given how short the removed segment is relative to the 302-aa protein. The sparse-autoencoder check also falls short of its magnitude threshold (top shared-feature shift 2.91 vs threshold 10.0), and while 21 features are gained/lost each, this count is stated to carry no interpretive weight on its own. Taken together, this category shows no evidence that losing this short N-terminal stretch alters domain content, biophysical character, or learned sequence features of the protein.
No diverging domains
Does the isoform gain or lose a real InterPro functional domain in the differential region (disorder/structural-only signatures excluded)? Gaining or losing a domain changes function directly.
Comparison
Domains & motifs (canonical vs isoform)
gained = only in the isoform; lost = only in the canonical
| Feature | Canonical | Isoform |
|---|---|---|
| InterPro domains | 7 | 7 |
| Short linear motifs | 3 | 3 |
less hydrophobic (-2.36) · more charged (+0.49) · more disordered (+0.08)
Biophysical character of the isoform-differential region versus the shared canonical core — pI, hydropathy, charge, disorder and related properties. Descriptive; the folding (P1) score keys off the GRAVY / charge / disorder deltas.
Comparison
Biophysics · differential vs shared region
highlighted rows are enriched in the differential region
| Property | Differential | Shared | Enrichment |
|---|---|---|---|
| Isoelectric point (pI) | 3.92 | 7.61 | 0.515 |
| Hydropathy (GRAVY) | -2.25 | 0.111 | -20.3 |
| Fraction charged | 0.75 | 0.255 | 2.94 |
| Disorder fraction | 0.143 | 0.0599 | 2.39 |
| Disorder-promoting | 0.75 | 0.52 | 1.44 |
| Low-complexity fraction | 0 | 0.0828 | 0 |
| Prion-like fraction | 0 | 0.212 | 0 |
| LLPS score | 0.0358 | 0.123 | 0.291 |
| π–π propensity | 0 | 0.189 | 0 |
| Aromaticity | 0 | 0.0795 | 0 |
| Instability index | -13.7 | 31 | -0.443 |
| Shannon entropy | 1.5 | 4.06 | 0.369 |
| Normalized complexity | 0.75 | 0.94 | 0.798 |
42 SAE features differ
Sparse-autoencoder (SAE) interpretability features on the ESM-C residual stream, comparing the isoform against the canonical protein. This is the S3 criterion — a presence check that fires when any interpretable feature is gained or lost. Only the top 30 features per category (ranked by activation, prevalence ≥ 2) are saved; each table shows the top 10 interpretable features, and generic / "unknown" features are hidden unless you expand it. What are SAE features? →
Part 1 · Global feature comparison
Which SAE features fire in the isoform vs the canonical protein, across the whole sequence.
Isoform-only features — 21 total (prevalence ≥ 2)
| Feature | Label | Description | Activation | Prevalence |
|---|---|---|---|---|
| #1162 | Short amphipathic interface helices | Short amphipathic alpha‑helical surface patches that serve as generic macromolecular interface elements (often contacting DNA/RNA or protein partners and frequently flanking/including catalytic acidic residues or metal‑binding positions) | 4.29 | 2 |
| #14603 | Charged amphipathic interaction helices | Charged, amphipathic alpha‑helical interaction segments—often N‑terminal and coiled‑coil‑like—that mediate protein–protein or protein–membrane contacts in small complex subunits and diverse enzymes/membrane proteins across taxa | 3.63 | 2 |
| #5495 | Elongated coiled-coil scaffolds | Long amphipathic alpha-helical coiled‑coil rod/stalk domains (heptad‑repeat scaffolds) that mediate dimerization/oligomerization and tethering in large cytoskeletal, membrane‑associated, and organellar assemblies | 2.74 | 2 |
| #825 | Mixed activation in short/fragment proteins | The feature activates broadly across short or fragment-length proteins from diverse origins, including both intrinsically disordered low-complexity regions and compact structured domains. It shows mixed regional and residue-level activation without strict preference for cleavage sites, signal/propeptide boundaries, or any single sequence context. | 2.42 | 2 |
| #5063 | Motif I SAM-binding loop | Conserved SAM/SAH-binding loop (motif I) of class I Rossmann-like S-adenosylmethionine-dependent methyltransferases: the short, often glycine-rich beta-to-alpha connecting loop that binds the SAM phosphate-ribose near the active site | 2.26 | 2 |
| #14081 | Disordered PPI motif regions | Intrinsically disordered, low‑complexity regions (IDRs) enriched in small/polar and acidic residues with frequent proline (including proline‑rich segments), marking protein–protein interaction modules that contain short linear motifs and transient alpha‑helical MoRFs, typically found in large scaffolds and regulatory tails across diverse taxa | 2.09 | 2 |
| #13118 | Alpha-solenoid and coiled-coil scaffolds | Alpha-helical repeat scaffolds in large eukaryotic proteins—principally HEAT/ARM-like alpha‑solenoids and long coiled‑coil rods used as assembly/tethering frameworks in nuclear transport, nucleoporins, and vesicle/endomembrane trafficking; the feature emphasizes structured helices and their termini rather than specific sequence motifs. | 2.06 | 2 |
| #1679 | DXPS C-terminal glycine-rich loop | A conserved glycine/basic-rich loop in the C-terminal domain of ThDP-dependent 1-deoxy-D-xylulose-5-phosphate (DXP) synthases and related transketolase-family carboligases. | 2.03 | 2 |
| #11257 | Phosphate-binding amphipathic helix | Short amphipathic alpha-helical segment that frequently serves as the phosphate-/nucleotide-binding helix immediately C-terminal to a glycine-rich phosphate-binding loop (P-loop or Rossmann-like), stabilizing ATP/ADP, nucleotide-sugar, or FAD/FMN pyrophosphate groups; when no such ligand is used, the feature selects a similar N-terminal helix with the same physicochemical profile. | 2.00 | 2 |
| #8538 | Sigma-70 region-2 helical scaffold | Amphipathic alpha-helical segments in well-ordered regions, with a strong specialization for the conserved helical core of sigma-70 region 2 in bacterial/organellar sigma factors; more generally, the feature marks long helices that serve as structural/interaction scaffolds across diverse proteins (regulatory, nucleic-acid–associated, proteostasis/translocation motors, and large modular biosynthetic enzymes). | 1.87 | 2 |
| #4173 | Conserved BAH domain segments | A BAH (Bromo-Adjacent Homology) domain feature that marks conserved internal segments of BAH domains in eukaryotic chromatin/DNA-associated proteins, including DNA cytosine-5 methyltransferases, origin recognition complex subunits, and related chromatin readers. | 1.84 | 4 |
| #8661 | Active-site rim loops | Short loop/helix-cap segments at secondary-structure boundaries that form the rim of catalytic or cofactor/substrate-binding pockets in enzyme domains (active-site–adjacent turns enriched in Gly/Pro with charged/aromatic residues), observed across diverse enzyme families | 1.83 | 2 |
| #8833 | N-terminal domain-capping helix | Short, charged N-terminal β→α structural module (an α-helix often immediately preceded by a β-strand/coil) that caps or initiates a domain (“domain N-cap/linker”) across diverse proteins, typically lying just ahead of the catalytic/core fold rather than at active-site residues. | 1.75 | 2 |
| #146 | Extended assembly interface regions | Extended, surface-exposed interaction regions—most commonly amphipathic alpha-helical stretches used for oligomerization/subunit packing and charged, low-complexity/disordered tails that act as activation/assembly segments; it can also highlight conserved flexible loops at binding interfaces (e.g., Ca2+-binding)—prevalent in subunits of large complexes and some enzymes across taxa. | 1.75 | 2 |
| #10360 | L7Ae-like RNA-binding patch | Short basic, glycine‑rich beta‑strand/loop surfaces that mediate nucleic‑acid (primarily RNA) recognition—most prominently the L7Ae/NHP2‑type RNA‑binding patch used in RNP assembly/processing and tRNA‑interacting enzymes—with occasional capture of analogous phosphate‑ligand binding strands in enzymes. | 1.73 | 2 |
| #7645 | Patchy structural-region peaks | A broad, sequence-context feature that fires in scattered patches across many diverse proteins, with peaks often falling in folded chain regions and at local structural boundaries rather than being restricted to any single fold class | 1.71 | 2 |
| #5508 | Broad N-terminal secondary-structure activation | Broad, near-whole-protein activation pattern that fires across much of compact and multidomain enzymes, especially anaerobic redox enzymes (aminomutases, reductases, CODH/ACS-type complexes) and pyrimidine/purine salvage/metabolism enzymes; activation is strongest over N-terminal folded regions and continues across long stretches of the chain. | 1.66 | 3 |
| #14103 | Histone-fold modules and tails | Histone-fold modules and their flanking histone-like tails across chromatin and transcription assemblies: the feature targets the three-helix histone-fold dimerization scaffold used by core/variant histones and histone-fold subunits of TFIID, SAGA/STAGA, NF‑Y, kinetochore MHF1/2, POLE3/POLE4, and viral histone doublets, often including adjacent Lys/Arg-rich (or subfamily-specific acidic) segments | 1.64 | 2 |
| #10588 | Short structured functional hotspots | A general marker of short, structured functional hotspots—most often alpha-helical elements within folded domains or transmembrane helices—that either contain or lie immediately adjacent to catalytic residues, DNA/ligand/metal-binding sites, protein–protein interaction/secretion motifs (e.g., ESX/WXG), or correspond to the bioactive mature segment of secreted peptides. | 1.61 | 2 |
| #14125 | Beta-strand N-cap motif | Beta-sheet entry/capping signal: the first 1–3 residues of beta-strands and the immediately preceding loop/turn (beta-strand N-cap/edge-of-sheet), often a Gly/Pro-containing turn feeding hydrophobic/aromatic residues at strand starts; a generic structural motif in well-structured cores rather than a specific functional site. | 1.61 | 2 |
| #11275 | Active-site lid/cofactor segment | A contiguous pocket-lining binding segment that forms or flanks enzyme active sites, typically a loop-to-helix region that includes or abuts the family signature motif and engages charged small molecules or cofactors (metal ions, phosphate-bearing ligands, porphyrins, flavins). These segments are often acidic and glycine-rich and act as active-site lids or cofactor-coordinating elements; in non-enzymes the feature analogously targets disordered tails used for partner/ligand interaction. | 1.57 | 2 |
Canonical-only features — 21 total (prevalence ≥ 2)
| Feature | Label | Description | Activation | Prevalence |
|---|---|---|---|---|
| #15264 | Asp-centered acidic catalytic motifs | Short, Asp-centered acidic motifs that coordinate Mg2+ and/or phosphate in catalytic or ligand‑binding sites—unifying phosphoryl/diester chemistry and anion-binding pockets (e.g., phospho‑Asp sites in REC domains, Walker‑B/DEAD acidic patches of NTPases, and HD/EAL/DHH catalytic motifs), with analogous Asp‑based ligand anchors in bacterial sensory/regulatory proteins; and in some acyl‑transferases (e.g., CoA‑transferases), catalytic Asp/Glu carboxylates that form acyl‑enzyme intermediates | 11.49 | 2 |
| #6354 | C5 methyltransferase helix motif | Recognition of a conserved helix within the SAM-dependent MTase C5-type domain of cytosine-C5 methyltransferases (DNMT2/Dcm-like and Type II cytosine MTases), corresponding to a structural element downstream of the catalytic Cys and SAM-binding residues rather than the catalytic/cofactor-binding residues themselves. | 4.98 | 2 |
| #10341 | Boundary and processing residues | A short linear boundary/processing microfeature: residues that mark solvent-exposed boundaries of structural/functional units—helix/coil or coil/strand linkers, helix termini, and peptide/domain edges—including proteolytic maturation junctions; generally outside buried cores and transmembrane segments. | 3.32 | 2 |
| #7317 | Oxyanion/metal-binding edge motif | A short, structured active‑site edge motif that brings together acidic residues (Asp/Glu, often as DE/ED pairs) with nearby basic residues (Arg/Lys/His), typically at a β‑strand→loop→α‑helix junction or strand–loop boundary, used to bind/stabilize an oxyanion (most often a phosphate/pyrophosphate or phosphodiester) and/or to coordinate catalytic metal ions across diverse phospho‑processing enzymes; the same physicochemical motif can appear in non‑enzymes. | 2.88 | 2 |
| #5232 | Short amphipathic helices | Short amphipathic alpha-helical segments that mediate assembly, nucleic-acid/protein binding, or membrane association; common in intrinsically disordered regions or flexible linkers, but also present as coiled-coils or small helix-bundles within otherwise structured proteins; occasionally overlap or flank transmembrane helices. Enriched in mixed charged and hydrophobic residues. | 2.79 | 2 |
| #9206 | Aromatic helix N-cap pocket rims | Aromatic- and histidine-enriched alpha-helix N-cap/loop-to-helix transition segments that scaffold the rims of ligand-binding and catalytic pockets; most prominent in carbohydrate-active enzymes but recurring across diverse enzyme folds. | 2.64 | 2 |
| #1920 | Alpha-helix proximal motifs | Short polar/hydrophobic motifs in or adjacent to alpha-helical segments of structured eukaryotic nuclear and trafficking proteins, frequently sitting near helix starts or within helix interiors of helical bundles and repeat-containing domains. | 2.41 | 5 |
| #12044 | Rossmann glycine-rich cofactor loop | Conserved Rossmann-like nucleotide-cofactor binding loop: the glycine-rich β1–α1 “GxGxxG/T” region and adjacent acidic residue that anchor the pyrophosphate/ribose of SAM, NAD, or FAD—most prominently motif I of class I SAM-dependent methyltransferases, but also the analogous loops of NAD/FAD-dependent oxidoreductases/monooxygenases. | 2.40 | 2 |
| #2856 | N-terminal Gly/Pro ATP-binding loop | N-terminal glycine/proline-containing loop preceding the ATP-grasp domain in ATP-dependent carboxylate–amine/peptide bond-forming ligases (ATP-grasp and Mur-like), but also captured in analogous gly/acidic loops of other NTP/cofactor-binding enzymes (e.g., NAD kinase, biotin carboxylase); typically centered on a G–P turn with an adjacent acidic residue (Glu/Asp), conserved across Bacteria, Archaea, and Eukaryota. | 2.32 | 2 |
| #3386 | AdoMet pocket PGG loop | Short glycine‑dipeptide loop (typically Pro–Gly–Gly or Lys–Pro–Gly–Gly, often flanked by basic residues) that forms a flexible turn at the edge of the AdoMet/dcAdoMet‑binding pocket in Rossmann‑like AdoMet‑utilizing enzymes—predominantly SAM‑dependent methyltransferases but also decarboxylated‑SAM aminopropyltransferases; a structural micro‑motif used to shape/close the cofactor/substrate site across diverse substrate specificities | 2.24 | 2 |
| #9096 | Intrinsically disordered low-complexity regions | Compositionally biased, intrinsically disordered low‑complexity segments (often short tandem‑repeat regions) enriched in small/flexible residues and sometimes cysteine/glutamine, commonly occurring in N‑terminal/propeptide stretches of secreted precursors and small unstructured proteins; peaks can also occur in flexible terminal/loop segments within otherwise structured proteins (including enzymes); peaks can fall at residues within simple repeats or immediately flanking processed peptide segments, but the unifying concept is IDR/low‑complexity or flexibly disordered segments rather than a specific domain. | 2.06 | 2 |
| #4120 | Helical docking and capping motifs | Alpha-helical interaction segments and their helix-capping/transition residues across diverse proteins, including conserved helical motifs in ribosomal proteins and partner-docking helices in cyclins | 1.95 | 2 |
| #1344 | PEST-like disordered tails/linkers | Intrinsically disordered, low-complexity regions enriched in acidic/Ser/Thr/Pro/Gln residues (PEST-like), typically functioning as cytosolic tails or inter-domain linkers. The feature is especially common adjacent to transmembrane helices and near (or just downstream of) RING-H2 zinc-finger domains in membrane E3 ubiquitin ligases, and more generally marks flexible loops bordering domain boundaries or conserved mobile catalytic motifs in large enzymes. | 1.92 | 2 |
| #11873 | Pro/Ser-rich domain-flanking IDRs | Intrinsically disordered, low‑complexity linker/tail regions enriched in Pro/Ser/Thr and polar/acidic residues (often containing SP/TP‑rich tracts) that flank or bridge structured domains; the feature avoids folded domains and preferentially marks boundary‑proximal IDRs used as flexible regulatory or tethering segments. | 1.90 | 2 |
| #2370 | Polar hotspots in structured segments | Charged/polar positions within structured segments of soluble globular proteins, including alpha-helical stretches and constrained loop regions (often within disulfide-bridged subdomains or near helix termini), that contribute to interaction or folding surfaces | 1.89 | 2 |
| #2003 | P-loop NTPase core detector | Core recognition of P-loop NTPase motor domains used across DNA-transaction enzymes, most prominently ASCE/RecA/AAA+-like ATPases (replicative helicases, strand-exchange/branch-migration, DNA packaging), but also extending to other NTP-driven machines (e.g., F1-ATPase) and select TRAFAC-class GTPases (e.g., FtsY/FlhF). The feature additionally activates on DnaG-type TOPRIM primases, likely via recognition of their nucleotide/metal-binding catalytic environment rather than a short motif. | 1.81 | 2 |
| #15654 | Phospho-regulatory low-complexity IDRs | Phospho-regulatory, low-complexity regions—intrinsically disordered or flexibly helical Ser/Thr- and charge-rich segments that mediate assembly/adaptor interactions—commonly found in eukaryotic proteins and largely excluded from catalytic cores and transmembrane helices. | 1.77 | 2 |
| #7181 | N-terminal cap/lid activation | N-terminal capping/lid subdomain adjacent to the active-site entrance of α/β enzymes—most prominently the enolase superfamily—highlighting helical/loop segments that shape substrate binding and gate access while sparing the catalytic metal-ligating residues and C‑terminal catalytic barrel | 1.77 | 2 |
| #7868 | Signal-peptide junction N-terminus | Signal-peptide–cleavage–adjacent N-terminal segments of secreted and extracellular proteins: the C-terminus of the signal peptide together with the immediately following propeptide/activation peptide or the first tens of residues of the mature ectodomain. These regions are common across secreted precursors and type I membrane proteins, often compositionally hydrophobic-to-mixed with occasional cysteines, frequently flexible/low-confidence but sometimes extending into the first structured element, and not tied to any specific fold or catalytic motif. | 1.70 | 2 |
| #5925 | N-terminal domain-onset leaders | Contiguous N‑terminal and early‑domain “leader” segments and peripheral loops that mark the onset or edge of a domain—often low‑complexity and/or transitioning from disorder into the first structured elements (helix/strand)—including pre‑SNARE helices, initial porin β‑strands after signal peptide cleavage, inter‑HEAT‑repeat linkers, and N‑terminal catalytic/interaction subdomains | 1.67 | 2 |
| #14141 | C-terminal TM helices and tail | C-terminal membrane module of polytopic membrane proteins: the last one to two transmembrane helices and the adjoining terminal cytosolic/lumenal tail, most prominently in lipid and cell‑envelope metabolic enzymes and intramembrane protease complexes. | 1.48 | 2 |
Shared features by |Δ| activation — 1495 total (prevalence ≥ 2)
| Feature | Label | Description | Δ activation | Iso act. | Canon act. | Iso prev. | Canon prev. |
|---|---|---|---|---|---|---|---|
| #10752 | Short solvent-exposed connector loops | Generic structural signal for short, solvent-exposed loop/turn connectors between secondary structure elements—especially beta-beta hairpin loops and helix-strand junctions—enriched in small/charged residues (S/T, N, D/E, K/R); often adjacent to functional sites but not family-specific | +1.48 | 3.56 | 2.09 | 18 | 15 |
| #3609 | Position-2 N-terminus residue detector | Detector of the identity of the second residue at the extreme N-terminus of proteins, with strongest preference for small residues (especially Ser, Ala, and Gly; also Thr/Pro), i.e., an N-terminal position-2 signal commonly associated with generic, disordered starts and co-translational N-terminus processing | -1.34 | 6.52 | 7.86 | 2 | 2 |
| #11860 | Peripheral domain boundary linkers | Short segments at domain boundaries and adjacent loops — often Pro-rich or acidic linker-like stretches, sometimes containing clustered Lys/Arg — that act as flexible linkers or peripheral, solvent-exposed elements rather than core catalytic motifs | -1.07 | 1.91 | 2.98 | 7 | 9 |
| #16250 | N-terminal first-helix motif | Onset of an N‑terminal alpha helix (N‑cap and first helical turn), typically marking the first helix of a helical hairpin/repeat unit (e.g., HTH/HEAT/EF‑hand/HhH) or an amphipathic transit helix, i.e., a generic structural “first-helix” motif rather than a specific function | -1.02 | 1.71 | 2.73 | 3 | 3 |
| #11395 | Spire KIND/WH2 with charged LCRs | Conserved motifs within the KIND domain and flanking the WH2 actin-binding motifs of Spire family actin nucleators, together with low-complexity, intrinsically disordered regions enriched in charged/polar residues (E/D/S/T/K/R) in other proteins; occasionally shows weaker signal within or flanking helical segments (e.g., transmembrane or coiled-coil boundaries). | -0.90 | 2.65 | 3.56 | 5 | 6 |
| #2234 | Eukaryotic N-terminal targeting signals | Eukaryotic N-terminal low-complexity, Ser/Thr- and Lys/Arg-rich leader segments that predominantly function as organelle-targeting presequences (especially chloroplast transit peptides), with spillover to mitochondrial targeting peptides, N-terminal peroxisomal PTS2 signals, and secretory signal peptides; the feature also activates on non-targeting disordered/basic N-termini in cytosolic proteins. | -0.73 | 2.85 | 3.58 | 9 | 12 |
| #2519 | Diffuse low-amplitude sequence-wide activation | Broadly distributed, low-amplitude feature that fires diffusely across many proteins, with frequent activation on polar residues (Thr, Ser) but also on charged and hydrophobic residues throughout both structured domains and disordered regions. | +0.71 | 4.52 | 3.81 | 8 | 8 |
| #15815 | Basic N-terminal targeting patch | Short, basic/polar N‑terminal leader/transit segment immediately after the initiator methionine (positions ~3–6) — i.e., the positively charged/polar start of signal peptides and organelle transit peptides, and more generally low‑acidic, disordered N‑terminal patches (including occasional cysteine‑rich starts) used for targeting, export, rRNA binding, or membrane topology cues | -0.65 | 3.81 | 4.46 | 3 | 3 |
| #5114 | Short N-terminal targeting arm | N-terminal segments (typically the first ~10 residues) across a wide range of bacterial, viral, and eukaryotic proteins. These are often signal/targeting/assembly arms, including RNA/DNA-binding tails, secretion/chaperone-binding regions, and assembly linkers. | +0.49 | 4.75 | 4.26 | 9 | 11 |
| #3299 | N-terminal targeting/pre-domain regions | Generic N-terminal leader/targeting and pre-domain segments: the model fires on the beginning-of-chain regions that encode export/targeting information (signal peptides; mitochondrial/chloroplast transit peptides) and on low-complexity/basic N-terminal tails or early amphipathic helices that precede the first structured/catalytic core; it can also extend into or occasionally recognize long internal helices that share the same physico-chemical profile. | -0.47 | 2.62 | 3.09 | 11 | 12 |
| #1143 | Transmembrane helices and flanks | Hydrophobic transmembrane alpha-helices and their immediately flanking residues; marks signal-anchor/first transmembrane helices in single-pass membrane proteins and internal transmembrane helices in multi-pass membrane proteins. | -0.46 | 3.19 | 3.65 | 3 | 4 |
| #7572 | Conserved catalytic helix motif | A conserved internal sequence/structural motif within enzyme catalytic domains, prominently exemplified by the "DRL(V/I)G(x)YEE" segment of the glutamate mutase epsilon subunit, where activation peaks on a short hydrophobic-aromatic stretch embedded in an α-helix close to cofactor/substrate binding residues. | -0.42 | 2.62 | 3.04 | 18 | 22 |
| #2363 | Charged alpha-helical tracts | Polar/charged alpha-helical tracts (often low-complexity): E/D/K/R/S/T/N/Q-rich, low-aromatic segments occurring both in intrinsically disordered regions and as solvent-exposed helices within folded domains; these amphipathic/coiled-coil–like helices mediate oligomerization, nucleic-acid/protein binding, and assembly, especially in viral proteins. | -0.42 | 2.70 | 3.11 | 2 | 4 |
| #3651 | C-terminal catalytic and tail modules | C-terminal functional modules of predominantly eukaryotic multidomain proteins—either (i) downstream catalytic cores in nucleic acid/protein–modifying enzymes or (ii) C-terminal interaction/trafficking tails in membrane proteins and cytosolic coat/adaptor scaffolds—characterized by long, compositionally biased segments (acidic, S/T/P/G-rich, often with multiple histidines) and not tied to a specific fold. | -0.36 | 1.88 | 2.24 | 7 | 9 |
| #1370 | Short low-complexity N-terminal segment | Short, low‑complexity, intrinsically disordered N‑terminal segments (~10–20 aa) that frequently correspond to leader/transit/propeptide presequences (e.g., chloroplast transit peptides, RiPP/bacteriocin leaders) or generic unstructured N‑tails; typically non‑hydrophobic and enriched in Ser/Thr/Pro but tolerant of basic (poly‑Arg/Lys) or Cys‑rich compositions | +0.36 | 2.05 | 1.70 | 2 | 2 |
| #7043 | Exposed helical scaffold surfaces | Exposed alpha-helical structural elements—particularly well-ordered helices and their N/C-capping positions—serving as generic interaction/scaffold surfaces (often charged), rather than family-specific catalytic motifs | -0.29 | 4.21 | 4.50 | 11 | 11 |
| #15683 | Pyruvate kinase helix-packing hydrophobes | Conserved hydrophobic residues within α-helical segments of bacterial pyruvate kinases, located at buried core/helix-packing positions rather than at catalytic or metal/substrate-binding sites. | -0.23 | 5.39 | 5.62 | 4 | 4 |
| #8494 | Alpha-helical hydrophobic packing | Generic structural signal of hydrophobic/aromatic residues within well-ordered alpha-helices of folded domains (helical packing/core or helix–helix interface positions), largely independent of specific catalytic sites or functions. | +0.22 | 5.63 | 5.41 | 12 | 15 |
| #3703 | Organelle mature domain activator | Mature, structured domains of organelle-targeted precursor proteins (predominantly plant chloroplast and mitochondrial), with strong preference for conserved functional cores (DNA/RNA‑binding motifs, catalytic folds, and transmembrane helices) and avoidance of N‑terminal transit peptides and extended low‑complexity tails. | +0.21 | 3.85 | 3.63 | 260 | 244 |
| #11911 | Short Lys/Arg-rich patches | Short sequence patches—often Lys/Arg-enriched and sometimes mixed with acidic residues—typically 8–25 residues long, frequently occurring in disordered N-terminal segments but also within ordered regions of diverse proteins, often associated with RNA/ribosome-contact surfaces or assembly interfaces. | -0.20 | 3.52 | 3.72 | 28 | 32 |
| #14782 | Plant cysteine synthase C-terminal motif | C-terminal tail motif of plant PLP-dependent cysteine synthases / O-acetylserine (thiol)-lyases, centered on a conserved "EAEN(M/L)" / "E(K/Q)M(K/Q)PE" signature near the very end of the polypeptide, with a weaker secondary signal on the internal "QGIGAG" loop of the same family. | -0.20 | 5.36 | 5.56 | 19 | 19 |
| #7534 | Alpha-helical interaction modules | Alpha-helical interaction elements in eukaryotic regulators—recognition helices and small helical bundles (e.g., homeobox/POU helices, bromodomains, OVATE), coiled-coils, and amphipathic helices that form macromolecular binding surfaces for DNA, chromatin marks, and protein partners; enriched at hydrophobic L/I/V/F positions with interspersed S/T/E/D | +0.19 | 3.58 | 3.39 | 2 | 3 |
| #1355 | Helix-capping interhelical hinges | Short coil/turn residues that cap or connect secondary-structure elements—especially interhelical loops and helix-capping positions—frequently at glycine or other helix‑breaking/helix‑capping residues and marking internal hinges; can also activate at isolated residues within compositionally biased or disordered segments. | -0.18 | 6.76 | 6.94 | 8 | 8 |
| #12004 | N-terminal Pro/His helical motifs | Short N-terminal sequence motifs in metabolic enzymes, characterized by Pro- and His-containing patches embedded in early α-helical segments (e.g. S-P-x-P-Y/F-H in aspartyl aminopeptidases; G-H-P-D in S-adenosylmethionine synthases) | -0.18 | 6.46 | 6.64 | 10 | 10 |
| #14534 | Unknown generic feature | Unknown generic feature | -2.91 | 13.55 | 16.45 | 240 | 243 |
| #4764 | Unknown generic feature | Unknown generic feature | +0.95 | 2.92 | 1.97 | 2 | 2 |
| #9194 | Unknown generic feature | Unknown generic feature | -0.30 | 13.05 | 13.34 | 287 | 289 |
| #14895 | Unknown generic feature | Unknown generic feature | -0.23 | 22.27 | 22.50 | 301 | 304 |
| #9005 | Unknown generic feature | Unknown generic feature | -0.20 | 13.48 | 13.68 | 194 | 200 |
| #1363 | Unknown generic feature | Unknown generic feature | -0.18 | 8.58 | 8.76 | 190 | 188 |
Part 2 · Differential coordinates
Features firing on just the canonical-lost (truncated) residues.
Unique-region features — 61 distinct (prevalence ≥ 2)
| Feature | Label | Description | Activation | Prevalence |
|---|---|---|---|---|
| #1108 | N-terminal amphipathic interaction helices | Long amphipathic alpha-helical segments, typically at the N-terminus, that serve as interaction/capping elements in soluble proteins (e.g., coiled-coil/connector helices in complexes, DNA-binding HTH helices, and helical lids adjacent to active sites), enriched in charged, helix-forming residues | 7.18 | 4 |
| #16150 | N-terminal leader and secondary structure | N-terminal leader segments and the immediate start of the first structured element (β-strand/α-helix) at protein starts (and occasionally at internal domain starts); in eukaryotic precursors this region frequently overlaps organellar transit peptides. | 6.78 | 4 |
| #11788 | Bacterial enzyme N-termini | Activates on N-terminal regions of bacterial/archaeal enzyme subunits, including both non-cleavable signal-anchor transmembrane helices of membrane-anchored redox subunits and N-terminal segments of soluble oxygenase/hydroxylase and cyclohydrolase subunits. | 6.74 | 4 |
| #1156 | Membrane-interfacial hydrophobic stretches | Extended hydrophobic/aromatic-rich secondary-structure runs—typically membrane-interfacial segments (transmembrane helices or outer-membrane beta-barrel strands) together with their immediate flanking loops, and, in soluble proteins, analogous hydrophobic helical/strand blocks at domain starts/ends or linkers (often following positive-inside/aromatic-boundary patterns). | 6.21 | 4 |
| #12273 | Noncatalytic regulatory appendages | Non-catalytic accessory regions outside enzyme or core folds—most commonly long N‑terminal regulatory tails and membrane‑proximal stems (including signal‑anchor TMs), but also internal helical scaffolds—enriched for low‑complexity, Ser/Thr- and acidic‑rich sequence and short linear motifs (e.g., phosphosites, CxxC). These segments mediate regulation, localization, or complex assembly and are consistently avoided at catalytic/metal‑binding active‑site residues. | 6.00 | 4 |
| #8003 | Polar low-complexity kinase IDRs | Broad, sequence-wide activation across eukaryotic lipid-metabolism kinases and NAD/NADH kinases, with the strongest peaks concentrated in disordered, low-complexity/polar-rich segments (often Ser/Thr/Pro/Gly-rich). The feature fires throughout the protein but reaches its maxima in compositionally biased, intrinsically disordered regions. | 5.47 | 4 |
| #5454 | Short alpha-helical segments | Short alpha-helical segments, including transmembrane and soluble helices adjacent to conserved regions; compositionally mixed charged (E/D/K/R) and hydrophobic (L/I/V/F) with frequent aromatics and Gly/Pro; occurs across soluble and membrane proteins | 4.96 | 2 |
| #9387 | Membrane helices and processing motifs | Membrane-targeting and insertion segments and their boundary/processing signals: the feature detects hydrophobic alpha-helical regions of signal peptides and transmembrane helices, with strongest response at helix–loop junctions at the membrane–water interface (often including aromatic anchor residues such as Trp/Tyr), and it also marks nearby trafficking/processing motifs (e.g., signal-peptide C-regions and dibasic convertase cleavage sites); weak activation can occur at helix starts of soluble domains. | 4.59 | 2 |
| #15815 | Basic N-terminal targeting patch | Short, basic/polar N‑terminal leader/transit segment immediately after the initiator methionine (positions ~3–6) — i.e., the positively charged/polar start of signal peptides and organelle transit peptides, and more generally low‑acidic, disordered N‑terminal patches (including occasional cysteine‑rich starts) used for targeting, export, rRNA binding, or membrane topology cues | 4.46 | 2 |
| #583 | Asp-biased disordered region detector | Detector of Asp residues embedded in low-complexity/disordered segments, with a strong bias for Asp over Glu; fires broadly in polar or acidic-enriched tracts and only weakly on isolated Asp in structured domains. | 4.20 | 2 |
| #4663 | Helical hydrophobic-aromatic binding motif | Conserved hydrophobic-aromatic motifs embedded in functional protein-protein and cofactor-binding sites, including the [4Fe-4S] cluster-binding region of archaeal DNA primase large subunit (PriL) and the CDK-binding "Speedy/Ringo box" of Speedy proteins | 4.12 | 3 |
| #5114 | Short N-terminal targeting arm | N-terminal segments (typically the first ~10 residues) across a wide range of bacterial, viral, and eukaryotic proteins. These are often signal/targeting/assembly arms, including RNA/DNA-binding tails, secretion/chaperone-binding regions, and assembly linkers. | 3.81 | 4 |
| #3056 | Rossmann SAM and P-loop motifs | SAM-dependent methyltransferases (primarily class I Rossmann-like, but also some SPOUT) and, more broadly, proteins with basic/polar N-terminal segments and gly/ser-rich or P-loop (Walker A) nucleotide-binding motifs common in nucleotide-dependent enzymes (including cofactor biosynthesis and other metabolic kinases); strongest representation in tetrapyrrole/corrinoid methylases and organelle-targeted precursors. | 3.80 | 4 |
| #7151 | N-terminal amphipathic helix start | N-terminal amphipathic alpha-helix initiation (the first helix and its N-cap/helix-start segment), marking the transition from a flexible N-terminus into the first stable helical element; a generic structural motif seen across diverse proteins and taxa, occasionally recurring at the starts of internal helices. | 3.78 | 2 |
| #6783 | Regulatory regions outside active sites | Long regions outside primary catalytic active sites — often N-terminal portions of multi-domain enzymes that include regulatory/accessory subdomains as well as some structured non-catalytic stretches. The feature consistently avoids conserved enzymatic active-site residues and metal/substrate binding motifs. | 3.71 | 4 |
| #617 | Glycoenzyme N-terminal anchor/stem | N-terminal targeting/anchoring “stem” of glycan-biosynthesis enzymes—especially glycosyltransferases—covering, depending on topology, the short cytosolic tail plus a type II signal‑anchor transmembrane helix and adjacent luminal/periplasmic stem, or the segment immediately C‑terminal to a cleavable signal peptide; more generally, the first helix/strand block preceding the catalytic core in glycan-pathway enzymes. | 3.64 | 4 |
| #6156 | Upstream noncatalytic acyltransferase helix | A conserved internal alpha-helical region of lipid acyltransferases, upstream of the catalytic HXXXXD motif. The feature marks a discrete helix in the soluble/membrane-associated acyltransferase fold that carries a recurring acidic/hydrophobic signature (D-R-x-L-L-D-V-E-D/E-P-F-x-F-x-P) rather than the catalytic motif itself. | 3.60 | 4 |
| #2234 | Eukaryotic N-terminal targeting signals | Eukaryotic N-terminal low-complexity, Ser/Thr- and Lys/Arg-rich leader segments that predominantly function as organelle-targeting presequences (especially chloroplast transit peptides), with spillover to mitochondrial targeting peptides, N-terminal peroxisomal PTS2 signals, and secretory signal peptides; the feature also activates on non-targeting disordered/basic N-termini in cytosolic proteins. | 3.58 | 4 |
| #11395 | Spire KIND/WH2 with charged LCRs | Conserved motifs within the KIND domain and flanking the WH2 actin-binding motifs of Spire family actin nucleators, together with low-complexity, intrinsically disordered regions enriched in charged/polar residues (E/D/S/T/K/R) in other proteins; occasionally shows weaker signal within or flanking helical segments (e.g., transmembrane or coiled-coil boundaries). | 3.56 | 2 |
| #12045 | Nucleotide phosphate-binding subdomain | A feature that marks a conserved internal region of the adenylation domain in AMP-forming acyl-CoA synthetases of the ANL superfamily, and may extend to analogous phosphate-coordinating subdomains in other α/β nucleotide-handling enzymes (e.g., Walker A P-loop NTPases, Rossmann-fold NAD(P)/SAM-binding enzymes, enolase-superfamily/metal-dependent phosphatases). | 3.50 | 4 |
| #9363 | Extreme N-terminal tail activation | N-terminal segments preceding the first structured catalytic domain—often disordered or coil-like and frequently enriched in hydrophobic/proline residues, though basic/low-complexity patches also activate. These regions correspond to leader/tail segments (e.g., cytosolic tails before a transmembrane helix, pre/pro-peptides, transit peptides, or conserved N-terminal extensions of catalytic chains). | 3.43 | 4 |
| #4485 | Hydrophobic alpha-helical segments | Hydrophobic alpha-helical segments in soluble globular proteins, prominently a conserved helix near the active site of glycoside hydrolase family 27 alpha-galactosidases. | 3.30 | 3 |
| #7265 | N-terminal initiator Met recognition | Recognition of the absolute protein N-terminus—specifically the initiator methionine (M1; often N-formylmethionine in bacteria/mitochondria) and the immediate +1 residue that becomes the mature N-terminus upon N-terminal methionine excision | 3.10 | 2 |
| #3299 | N-terminal targeting/pre-domain regions | Generic N-terminal leader/targeting and pre-domain segments: the model fires on the beginning-of-chain regions that encode export/targeting information (signal peptides; mitochondrial/chloroplast transit peptides) and on low-complexity/basic N-terminal tails or early amphipathic helices that precede the first structured/catalytic core; it can also extend into or occasionally recognize long internal helices that share the same physico-chemical profile. | 3.09 | 4 |
| #9214 | Unknown generic feature | Unknown generic feature | 18.92 | 4 |
| #14895 | Unknown generic feature | Unknown generic feature | 18.50 | 4 |
| #1803 | Unknown generic feature | Unknown generic feature | 16.61 | 4 |
| #14534 | Unknown generic feature | Unknown generic feature | 16.45 | 4 |
| #9194 | Unknown generic feature | Unknown generic feature | 13.34 | 4 |
| #9005 | Unknown generic feature | Unknown generic feature | 10.75 | 4 |
Top-K sparse-autoencoder activations on the ESM-C residual stream. Activation is a feature's peak value over its region; Prevalence is the number of residues it fires on; Δ activation is isoform − canonical. Only the top 30 features per category are saved; generic / "unknown" features are hidden until you expand a table. Read more about SAE features →
Clinical variants
Differential region — lost N-terminus (canonical-only)
| Pos (iso) | AA change | Consequence | Source | Clin. sig. | AF (gnomAD) | Impact | AlphaMissense | ESM-C ΔLLR | Link |
|---|---|---|---|---|---|---|---|---|---|
| — | D→D | intronic | gnomAD | — | 1.78e-05 | — | — | 0.00 | chr12-123633549-G-A |
| — | D→Y | intronic | gnomAD | — | 1.19e-04 | — | likely_benign (0.18) | -5.67 | chr12-123633551-C-A |
| — | D→H | intronic | gnomAD | — | 1.16e-05 | — | likely_benign (0.15) | -3.36 | chr12-123633551-C-G |
| — | D→N | intronic | gnomAD | — | 6.85e-07 | — | likely_benign (0.08) | -1.03 | chr12-123633551-C-T |
| — | D→H | intronic | gnomAD | — | 6.85e-07 | — | likely_benign (0.22) | -5.42 | chr12-123633554-C-G |
| — | D→N | intronic | gnomAD | — | 6.85e-07 | — | likely_benign (0.08) | -2.21 | chr12-123633554-C-T |
| — | M→V | intronic | gnomAD | — | 6.85e-07 | — | — | -6.96 | chr12-123633557-T-C |
| — | D→Y | intronic | ClinVar | Uncertain significance | — | — | likely_benign (0.18) | -5.67 | ClinVar:813657 |
8 variants in the differential region.
Shared canonical core — sequence common to canonical and isoform; AlphaMissense applies here
| Pos (iso) | AA change | Consequence | Source | Clin. sig. | AF (gnomAD) | Impact | AlphaMissense | ESM-C ΔLLR | Link |
|---|---|---|---|---|---|---|---|---|---|
| 0 | K→K | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123633546-C-T |
| 0 | — | inframe_deletion | gnomAD | — | 6.84e-07 | — | — | — | chr12-123633548-TGTC-T |
| 1 | E→E | synonymous_variant | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123632445-C-T |
| 1 | E→K | missense_variant | gnomAD | — | 1.23e-05 | — | likely_benign (0.17) | -4.77 | chr12-123633545-C-T |
| 1 | E→K | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.17) | -4.77 | ClinVar:2176384 |
| 1 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2877544 |
| 2 | L→S | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.77) | -4.98 | ClinVar:2296169 |
| 3 | I→T | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.06) | -2.15 | chr12-123632440-A-G |
| 3 | I→V | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | 1.15 | chr12-123632441-T-C |
| 4 | E→* | stop_gained | COSMIC | — | — | LoF | — | — | COSV106331808 |
| 5 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123632433-GTA-G |
| 5 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2874636 |
| 5 | Y→Y | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3692403 |
| 6 | F→S | missense_variant | gnomAD | — | 6.16e-06 | damaging | likely_pathogenic (0.97) | -9.11 | chr12-123632431-A-G |
| 6 | F→I | missense_variant | gnomAD | — | 6.85e-07 | damaging | likely_pathogenic (0.87) | -8.79 | chr12-123632432-A-T |
| 7 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123632427-CTT-C |
| 7 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123632427-CTTAAAGTA-C |
| 7 | K→E | missense_variant | gnomAD | — | 4.79e-06 | — | likely_benign (0.10) | -3.16 | chr12-123632429-T-C |
| 7 | — | frameshift_variant | gnomAD | — | 6.85e-07 | LoF | — | — | chr12-123632429-T-TA |
| 7 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2962147 |
| 8 | S→F | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.13) | -3.95 | chr12-123632425-G-A |
| 8 | S→C | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -3.64 | chr12-123632425-G-C |
| 9 | Q→H | missense_variant | gnomAD | — | 6.57e-05 | — | likely_benign (0.28) | -4.98 | chr12-123632421-C-G |
| 9 | Q→Q | synonymous_variant | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123632421-C-T |
| 9 | Q→H | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.28) | -4.98 | ClinVar:2185148 |
| 9 | Q→R | missense_variant | COSMIC | — | — | — | likely_benign (0.12) | -4.32 | COSV99967622 |
| 10 | — | frameshift_variant | gnomAD | — | 2.05e-06 | LoF | — | — | chr12-123632418-C-CA |
| 10 | M→I | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.28) | -1.50 | chr12-123632418-C-T |
| 10 | M→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.28) | -1.50 | ClinVar:1345195 |
| 10 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2858770 |
| 11 | K→K | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123632415-T-C |
| 11 | K→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | 0.66 | chr12-123632416-T-C |
| 12 | E→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | -3.62 | chr12-123632413-T-G |
| 12 | E→K | missense_variant | COSMIC | — | — | — | likely_benign (0.09) | -3.59 | COSV99967654 |
| 13 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123632411-CTTCT-C |
| 14 | P→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.15) | -4.97 | chr12-123632407-G-C |
| 14 | P→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.10) | -4.84 | chr12-123632408-G-C |
| 16 | M→V | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.08) | -1.69 | chr12-123632402-T-C |
| 16 | M→T | missense_variant | COSMIC | — | — | — | likely_benign (0.14) | -4.32 | COSV57459585 |
| 17 | A→A | synonymous_variant | gnomAD | — | 6.23e-05 | — | — | 0.00 | chr12-123632397-G-A |
| 17 | A→V | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.70) | -5.98 | chr12-123632398-G-A |
| 17 | A→P | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.29) | -5.80 | chr12-123632399-C-G |
| 17 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1621049 |
| 18 | S→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123632395-G-C |
| 18 | S→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2767181 |
| 18 | S→S | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57459031 |
| 19 | A→A | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123632391-T-C |
| 21 | A→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -5.36 | chr12-123632387-C-A |
| 22 | A→A | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123632382-G-A |
| 22 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2961048 |
| 23 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632379-G-A |
| 23 | I→M | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.31) | -6.30 | chr12-123632379-G-C |
| 23 | I→N | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.94) | -8.61 | chr12-123632380-A-T |
| 24 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632376-C-A |
| 24 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632376-C-G |
| 24 | R→Q | missense_variant | gnomAD | — | 2.53e-05 | — | likely_benign (0.10) | -4.94 | chr12-123632377-C-T |
| 24 | R→W | missense_variant | gnomAD | — | 5.47e-05 | — | likely_benign (0.28) | -7.19 | chr12-123632378-G-A |
| 24 | R→W | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.28) | -7.19 | ClinVar:1386755 |
| 24 | R→Q | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.10) | -4.94 | ClinVar:1915443 |
| 24 | R→W | missense_variant | COSMIC | — | — | — | likely_benign (0.28) | -7.19 | COSV57459867 |
| 25 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632373-C-A |
| 25 | T→T | synonymous_variant | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123632373-C-T |
| 25 | T→M | missense_variant | gnomAD | — | 5.47e-06 | damaging | ambiguous (0.40) | -7.62 | chr12-123632374-G-A |
| 25 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2875935 |
| 25 | T→M | missense_variant | COSMIC | — | — | damaging | ambiguous (0.40) | -7.62 | COSV57459816 |
| 25 | T→S | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -3.75 | COSV57459822 |
| 29 | F→F | synonymous_variant | gnomAD | — | 6.85e-07 | — | — | 0.00 | chr12-123632361-G-A |
| 29 | F→F | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2998111 |
| 30 | L→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.75) | -6.32 | COSV57459800 |
| 31 | K→N | missense_variant | gnomAD | — | 6.86e-07 | — | ambiguous (0.45) | -5.51 | chr12-123632355-C-A |
| 31 | K→K | synonymous_variant | gnomAD | — | 2.06e-06 | — | — | 0.00 | chr12-123632355-C-T |
| 31 | K→K | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2832238 |
| 31 | K→N | missense_variant | COSMIC | — | — | — | ambiguous (0.45) | -5.51 | COSV99967567 |
| 32 | — | frameshift_variant | gnomAD | — | 6.86e-07 | LoF | — | — | chr12-123632353-CTCTT-C |
| 32 | R→T | missense_variant | COSMIC | — | — | — | likely_benign (0.14) | -6.80 | COSV57458514 |
| 33 | D→H | missense_variant | gnomAD | — | 6.88e-07 | damaging | likely_pathogenic (0.76) | -6.14 | chr12-123632351-C-G |
| 33 | D→H | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.76) | -6.14 | ClinVar:1976823 |
| 34 | K→E | missense_variant | gnomAD | — | 2.06e-06 | — | likely_benign (0.08) | -3.62 | chr12-123632348-T-C |
| 35 | G→E | missense_variant | gnomAD | — | 6.85e-07 | — | ambiguous (0.34) | -3.34 | chr12-123630533-C-T |
| 35 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2826906 |
| 35 | G→R | missense_variant | ClinVar | — | — | damaging | likely_pathogenic (0.63) | -6.69 | ClinVar:4381679 |
| 36 | E→D | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -3.13 | COSV57458205 |
| 36 | — | mnv | COSMIC | — | — | — | — | — | COSV104564172 |
| 37 | T→A | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.87) | -7.31 | COSV108005029 |
| 38 | I→M | missense_variant | gnomAD | — | 6.85e-07 | — | likely_benign (0.18) | -3.83 | chr12-123630523-G-C |
| 38 | I→V | missense_variant | gnomAD | — | 6.85e-06 | — | likely_benign (0.11) | -3.40 | chr12-123630525-T-C |
| 38 | I→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.11) | -3.40 | ClinVar:1480504 |
| 39 | Q→R | missense_variant | gnomAD | — | 6.85e-07 | — | likely_benign (0.25) | -5.98 | chr12-123630521-T-C |
| 40 | G→D | missense_variant | ClinVar | Likely pathogenic | — | damaging | likely_pathogenic (0.76) | -4.81 | ClinVar:2443120 |
| 41 | L→L | synonymous_variant | gnomAD | — | 6.85e-07 | — | — | 0.00 | chr12-123630514-C-G |
| 42 | R→R | synonymous_variant | gnomAD | — | 4.11e-06 | — | — | 0.00 | chr12-123630513-T-G |
| 42 | R→R | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2719860 |
| 43 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630508-C-G |
| 43 | A→A | synonymous_variant | gnomAD | — | 3.42e-06 | — | — | 0.00 | chr12-123630508-C-T |
| 43 | A→V | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.13) | -0.89 | chr12-123630509-G-A |
| 43 | A→T | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.08) | -1.75 | chr12-123630510-C-T |
| 43 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2976088 |
| 43 | A→A | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57460265 |
| 43 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.13) | -0.89 | COSV99967503 |
| 44 | N→D | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.16) | -4.94 | chr12-123630507-T-C |
| 45 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630502-G-A |
| 45 | L→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.68) | -6.74 | COSV57458047 |
| 46 | T→T | synonymous_variant | gnomAD | — | 3.08e-05 | — | — | 0.00 | chr12-123630499-G-C |
| 46 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:753274 |
| 48 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.20) | -5.10 | chr12-123630495-C-T |
| 48 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.29) | -4.69 | COSV99967521 |
| 49 | I→M | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -4.86 | chr12-123630490-T-C |
| 49 | I→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | -3.81 | chr12-123630492-T-C |
| 50 | E→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.24) | -5.71 | ClinVar:4247691 |
| 51 | T→T | synonymous_variant | gnomAD | — | 4.10e-06 | — | — | 0.00 | chr12-123630484-G-C |
| 51 | T→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -3.18 | chr12-123630486-T-A |
| 51 | T→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -3.04 | chr12-123630486-T-C |
| 51 | T→S | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.13) | -3.18 | ClinVar:1507295 |
| 52 | L→L | synonymous_variant | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123630481-C-G |
| 52 | L→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -9.79 | chr12-123630482-A-G |
| 52 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3003025 |
| 52 | L→M | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -5.07 | COSV99967509 |
| 53 | C→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:3639835 |
| 54 | G→G | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630475-A-G |
| 55 | V→A | missense_variant | gnomAD | — | 5.66e-04 | — | likely_benign (0.13) | -3.56 | chr12-123630473-A-G |
| 55 | V→A | missense_variant | ClinVar | Benign/Likely benign | — | — | likely_benign (0.13) | -3.56 | ClinVar:883546 |
| 55 | V→A | missense_variant | COSMIC | — | — | — | likely_benign (0.13) | -3.56 | COSV57459432 |
| 56 | D→H | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.80) | -6.95 | chr12-123630471-C-G |
| 57 | S→F | missense_variant | gnomAD | — | 1.37e-06 | — | ambiguous (0.44) | -5.57 | chr12-123630467-G-A |
| 58 | S→F | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.79) | -7.59 | chr12-123630464-G-A |
| 59 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630460-C-T |
| 59 | V→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.68) | -5.61 | chr12-123630462-C-A |
| 60 | A→A | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630457-T-G |
| 60 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1906785 |
| 61 | V→A | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.78) | -6.86 | chr12-123630455-A-G |
| 63 | S→S | synonymous_variant | gnomAD | — | 7.94e-05 | — | — | 0.00 | chr12-123630448-A-G |
| 63 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2977946 |
| 63 | S→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.98) | -9.37 | COSV57459760 |
| 63 | S→C | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.59) | -8.25 | COSV99967639 |
| 64 | G→G | synonymous_variant | gnomAD | — | 3.83e-05 | — | — | 0.00 | chr12-123630445-G-A |
| 64 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630445-G-T |
| 64 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.77) | -8.56 | chr12-123630446-C-A |
| 64 | G→S | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.40) | -6.71 | chr12-123630447-C-T |
| 64 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2974054 |
| 65 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630442-C-A |
| 65 | G→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -5.95 | chr12-123630443-C-G |
| 65 | G→R | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.97) | -7.48 | chr12-123630444-C-T |
| 65 | G→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.97) | -7.48 | ClinVar:3375980 |
| 68 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -6.24 | chr12-123630433-G-T |
| 68 | F→F | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57458307 |
| 70 | R→R | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630427-G-A |
| 70 | R→H | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.57) | -6.30 | chr12-123630428-C-T |
| 70 | R→R | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2083276 |
| 71 | F→F | synonymous_variant | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123630424-G-A |
| 71 | F→F | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2978592 |
| 71 | F→L | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.99) | -7.00 | COSV57459047 |
| 72 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630421-G-A |
| 72 | I→I | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57459564 |
| 72 | I→M | missense_variant | COSMIC | — | — | — | ambiguous (0.51) | -6.42 | COSV57458414 |
| 72 | — | inframe_deletion | COSMIC | — | — | — | — | — | COSV57460141 |
| 74 | L→V | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.46) | -6.86 | chr12-123630417-G-C |
| 74 | L→I | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.45) | -7.24 | chr12-123630417-G-T |
| 75 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630412-G-A |
| 75 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | 3.34 | chr12-123630414-C-T |
| 75 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3701756 |
| 76 | S→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -3.84 | ClinVar:2124902 |
| 76 | S→S | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57458728 |
| 76 | S→F | missense_variant | COSMIC | — | — | — | ambiguous (0.48) | -4.12 | COSV99967684 |
| 77 | L→L | synonymous_variant | gnomAD | — | 4.38e-05 | — | — | 0.00 | chr12-123630408-G-A |
| 77 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1638519 |
| 77 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2778378 |
| 78 | E→E | synonymous_variant | gnomAD | — | 6.16e-06 | — | — | 0.00 | chr12-123630403-T-C |
| 78 | E→Q | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.41) | -5.31 | chr12-123630405-C-G |
| 78 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1938019 |
| 79 | Y→Y | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123630400-G-A |
| 79 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630402-A-AC |
| 80 | S→S | synonymous_variant | gnomAD | — | 1.30e-05 | — | — | 0.00 | chr12-123630397-G-A |
| 80 | S→C | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.16) | -6.30 | chr12-123630398-G-C |
| 80 | S→S | synonymous_variant | ClinVar | Uncertain significance | — | — | — | 0.00 | ClinVar:593688 |
| 80 | S→F | missense_variant | COSMIC | — | — | — | likely_benign (0.30) | -6.67 | COSV57459824 |
| 81 | D→E | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.28) | -2.87 | chr12-123630283-A-T |
| 81 | D→V | missense_variant | gnomAD | — | 1.37e-06 | damaging | ambiguous (0.48) | -8.19 | chr12-123630284-T-A |
| 82 | Y→Y | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630280-G-A |
| 82 | Y→S | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.35) | -1.47 | chr12-123630281-T-G |
| 82 | Y→Y | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2778868 |
| 82 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2828613 |
| 85 | C→R | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.91) | -6.12 | COSV57459610 |
| 86 | K→R | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.10) | -3.44 | chr12-123630269-T-C |
| 86 | — | frameshift_variant | COSMIC | — | — | LoF | — | — | COSV104391797 |
| 87 | K→K | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630265-C-T |
| 88 | I→M | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.11) | -2.85 | chr12-123630262-G-C |
| 88 | I→N | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -3.80 | chr12-123630263-A-T |
| 88 | I→V | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.09) | -0.03 | chr12-123630264-T-C |
| 89 | M→K | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.93) | -9.19 | COSV104564174 |
| 90 | I→T | missense_variant | gnomAD | — | 6.16e-06 | — | likely_benign (0.10) | -3.50 | chr12-123630257-A-G |
| 91 | E→D | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -0.03 | chr12-123630253-C-G |
| 91 | E→E | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630253-C-T |
| 91 | E→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.17) | -4.98 | chr12-123630254-T-C |
| 91 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123630255-C-CA |
| 91 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:4807060 |
| 92 | R→Q | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.60) | -5.36 | chr12-123630251-C-T |
| 92 | R→W | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.87) | -7.74 | chr12-123630252-G-A |
| 92 | R→Q | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.60) | -5.36 | COSV99967535 |
| 93 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630247-T-TC |
| 93 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630247-TC-T |
| 93 | G→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -7.71 | ClinVar:3087891 |
| 94 | E→K | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.14) | -5.37 | chr12-123630246-C-T |
| 94 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630246-CT-C |
| 94 | E→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2846761 |
| 95 | L→V | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.11) | -0.34 | chr12-123630243-G-C |
| 97 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630235-G-A |
| 97 | L→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.97) | -9.60 | chr12-123630236-A-G |
| 98 | R→S | missense_variant | gnomAD | — | 2.05e-06 | — | likely_benign (0.20) | -2.34 | chr12-123630232-C-A |
| 99 | — | inframe_deletion | gnomAD | — | 7.52e-06 | — | — | — | chr12-123630229-TCTC-T |
| 99 | R→T | missense_variant | gnomAD | — | 6.84e-06 | — | ambiguous (0.46) | -3.03 | chr12-123630230-C-G |
| 99 | R→K | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | 3.09 | chr12-123630230-C-T |
| 99 | — | inframe_deletion | ClinVar | Uncertain significance | — | — | — | — | ClinVar:1933346 |
| 99 | R→G | missense_variant | COSMIC | — | — | — | ambiguous (0.50) | -6.78 | COSV99967524 |
| 100 | I→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.11) | -3.22 | chr12-123630228-T-C |
| 101 | S→S | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630223-T-A |
| 101 | S→P | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (0.68) | -7.69 | chr12-123630225-A-G |
| 101 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2991250 |
| 102 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630222-G-A |
| 103 | S→S | synonymous_variant | gnomAD | — | 6.16e-06 | — | — | 0.00 | chr12-123630217-T-C |
| 103 | S→S | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123630217-T-G |
| 103 | S→L | missense_variant | gnomAD | — | 5.47e-06 | damaging | ambiguous (0.56) | -7.56 | chr12-123630218-G-A |
| 103 | S→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630218-G-C |
| 103 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1632053 |
| 103 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1938791 |
| 103 | S→L | missense_variant | ClinVar | Uncertain significance | — | damaging | ambiguous (0.56) | -7.56 | ClinVar:1964945 |
| 103 | S→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2719446 |
| 104 | R→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.91) | -10.49 | chr12-123630215-C-A |
| 104 | R→K | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.53) | -6.06 | chr12-123630215-C-T |
| 104 | R→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630216-T-A |
| 104 | R→G | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.85) | -7.99 | chr12-123630216-T-C |
| 105 | N→N | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630211-G-A |
| 106 | K→E | missense_variant | ClinVar | Pathogenic | — | — | ambiguous (0.46) | -6.91 | ClinVar:217279 |
| 107 | I→I | synonymous_variant | gnomAD | — | 8.21e-06 | — | — | 0.00 | chr12-123630205-A-G |
| 107 | I→T | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.61) | -5.74 | chr12-123630206-A-G |
| 107 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630206-AT-A |
| 109 | D→D | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123630199-A-G |
| 109 | D→Y | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.15) | -3.72 | chr12-123630201-C-A |
| 109 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2753789 |
| 110 | L→P | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.93) | -9.08 | chr12-123630197-A-G |
| 110 | L→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -5.52 | chr12-123630198-G-C |
| 111 | C→C | synonymous_variant | gnomAD | — | 6.16e-06 | — | — | 0.00 | chr12-123630193-G-A |
| 111 | C→C | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3003887 |
| 112 | H→H | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630190-A-G |
| 112 | H→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -5.74 | chr12-123630191-T-A |
| 112 | H→D | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.25) | -7.18 | chr12-123630192-G-C |
| 112 | H→N | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.10) | -5.30 | chr12-123630192-G-T |
| 112 | H→H | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2701929 |
| 113 | T→A | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | -2.87 | chr12-123630189-T-C |
| 114 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630184-G-GA |
| 114 | — | inframe_deletion | gnomAD | — | 1.37e-06 | — | — | — | chr12-123630184-GAAA-G |
| 115 | I→F | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.50) | -7.47 | chr12-123630183-T-A |
| 115 | I→L | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.23) | -6.41 | ClinVar:3380131 |
| 116 | K→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.26) | -4.88 | chr12-123630179-T-G |
| 116 | K→E | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -4.97 | chr12-123630180-T-C |
| 117 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2891533 |
| 118 | G→G | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630172-T-C |
| 118 | G→G | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630172-T-G |
| 118 | G→E | missense_variant | gnomAD | — | 3.63e-05 | damaging | likely_pathogenic (0.58) | -2.85 | chr12-123630173-C-T |
| 118 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2845940 |
| 119 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630169-C-A |
| 119 | A→A | synonymous_variant | gnomAD | — | 1.37e-05 | — | — | 0.00 | chr12-123630169-C-T |
| 119 | A→V | missense_variant | gnomAD | — | 1.10e-05 | — | likely_benign (0.25) | -4.46 | chr12-123630170-G-A |
| 119 | A→A | synonymous_variant | ClinVar | — | — | — | — | 0.00 | ClinVar:4381678 |
| 119 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.25) | -4.46 | COSV108005073 |
| 120 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627154-T-C |
| 120 | T→A | missense_variant | gnomAD | — | 1.98e-05 | — | likely_benign (0.11) | -4.25 | chr12-123627156-T-C |
| 121 | I→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -5.37 | chr12-123627153-T-A |
| 121 | I→V | missense_variant | gnomAD | — | 8.21e-06 | — | likely_benign (0.09) | -1.56 | chr12-123627153-T-C |
| 121 | I→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.09) | -1.56 | ClinVar:4017108 |
| 122 | L→F | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.41) | -6.32 | chr12-123627148-C-A |
| 122 | L→S | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -11.47 | chr12-123627149-A-G |
| 122 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:721731 |
| 122 | L→L | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV101424582 |
| 123 | T→T | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627145-A-C |
| 123 | T→T | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV71194134 |
| 124 | H→H | synonymous_variant | gnomAD | — | 4.86e-05 | — | — | 0.00 | chr12-123627142-G-A |
| 124 | — | frameshift_variant | gnomAD | — | 4.79e-06 | LoF | — | — | chr12-123627142-G-GT |
| 124 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2802843 |
| 124 | H→H | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2898580 |
| 124 | H→H | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV71194586 |
| 125 | A→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.91) | -7.55 | chr12-123627140-G-A |
| 125 | A→T | missense_variant | gnomAD | — | 2.39e-05 | — | ambiguous (0.52) | -2.23 | chr12-123627141-C-T |
| 125 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.52) | -2.23 | ClinVar:2689011 |
| 125 | A→T | missense_variant | COSMIC | — | — | — | ambiguous (0.52) | -2.23 | COSV71193843 |
| 126 | Y→C | missense_variant | gnomAD | — | 2.05e-06 | — | likely_benign (0.14) | -2.72 | chr12-123627137-T-C |
| 126 | Y→C | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.14) | -2.72 | ClinVar:548549 |
| 127 | S→S | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627133-G-A |
| 127 | S→F | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.99) | -10.62 | chr12-123627134-G-A |
| 127 | S→F | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -10.62 | ClinVar:3068028 |
| 127 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:4766714 |
| 128 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627130-T-C |
| 128 | R→K | missense_variant | COSMIC | — | — | — | ambiguous (0.35) | -6.37 | COSV107522310 |
| 129 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627127-C-T |
| 130 | V→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.89) | -6.65 | chr12-123627126-C-G |
| 130 | V→L | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.89) | -6.65 | ClinVar:4743250 |
| 130 | V→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.93) | -9.55 | COSV71194509 |
| 131 | L→V | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.17) | -6.18 | chr12-123627123-G-C |
| 133 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627115-G-C |
| 133 | V→V | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV71194283 |
| 134 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627112-C-G |
| 134 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123627112-C-T |
| 134 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2820826 |
| 135 | E→E | synonymous_variant | gnomAD | — | 8.13e-04 | — | — | 0.00 | chr12-123627109-T-C |
| 135 | E→V | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.39) | -7.38 | chr12-123627110-T-A |
| 135 | E→E | synonymous_variant | ClinVar | Benign | — | — | — | 0.00 | ClinVar:307529 |
| 137 | A→A | synonymous_variant | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123627103-G-A |
| 137 | A→V | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.60) | -6.40 | chr12-123627104-G-A |
| 137 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.54) | -6.05 | chr12-123627105-C-T |
| 137 | A→V | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.60) | -6.40 | ClinVar:1465594 |
| 137 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1650516 |
| 137 | A→V | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.60) | -6.40 | COSV71194272 |
| 138 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627100-C-T |
| 138 | V→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -5.05 | chr12-123627102-C-G |
| 138 | V→M | missense_variant | gnomAD | — | 3.22e-05 | — | likely_benign (0.17) | -5.62 | chr12-123627102-C-T |
| 138 | V→M | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.17) | -5.62 | ClinVar:1486551 |
| 139 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627097-C-G |
| 139 | A→A | synonymous_variant | gnomAD | — | 9.47e-04 | — | — | 0.00 | chr12-123627097-C-T |
| 139 | A→V | missense_variant | gnomAD | — | 1.30e-05 | — | likely_benign (0.09) | -2.58 | chr12-123627098-G-A |
| 139 | A→A | synonymous_variant | ClinVar | Benign/Likely benign | — | — | — | 0.00 | ClinVar:425020 |
| 139 | A→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.09) | -2.58 | ClinVar:1467898 |
| 140 | A→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -5.05 | chr12-123627095-G-A |
| 140 | A→T | missense_variant | gnomAD | — | 1.85e-05 | — | likely_benign (0.10) | -4.61 | chr12-123627096-C-T |
| 140 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.10) | -4.61 | ClinVar:806960 |
| 140 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2018522 |
| 140 | A→G | missense_variant | COSMIC | — | — | — | likely_benign (0.12) | -4.33 | COSV71194527 |
| 140 | A→T | missense_variant | COSMIC | — | — | — | likely_benign (0.10) | -4.61 | COSV71193807 |
| 141 | K→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123627093-T-A |
| 141 | K→N | missense_variant | COSMIC | — | — | — | likely_benign (0.24) | -2.37 | COSV101424580 |
| 142 | K→M | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.59) | -8.62 | chr12-123627089-T-A |
| 143 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627085-T-C |
| 143 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627085-T-G |
| 143 | R→Q | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.23) | -4.65 | chr12-123627086-C-T |
| 143 | R→* | stop_gained | gnomAD | — | 8.55e-05 | LoF | — | — | chr12-123627087-G-A |
| 143 | R→* | stop_gained | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:995942 |
| 143 | R→R | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2826822 |
| 143 | R→Q | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.23) | -4.65 | ClinVar:3087892 |
| 143 | R→Q | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -4.65 | COSV71193772 |
| 143 | R→* | stop_gained | COSMIC | — | — | LoF | — | — | COSV101424587 |
| 144 | F→L | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.95) | -4.94 | ClinVar:3087893 |
| 145 | S→S | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627079-A-G |
| 145 | S→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.19) | -5.87 | chr12-123627080-C-A |
| 145 | S→T | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.07) | -2.19 | chr12-123627080-C-G |
| 145 | S→N | missense_variant | gnomAD | — | 2.53e-05 | — | likely_benign (0.12) | -2.47 | chr12-123627080-C-T |
| 145 | S→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -6.96 | chr12-123627081-T-C |
| 146 | V→V | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627076-T-C |
| 146 | V→A | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.65) | -6.86 | chr12-123627077-A-G |
| 146 | V→L | missense_variant | gnomAD | — | 1.09e-05 | damaging | likely_pathogenic (0.71) | -6.49 | chr12-123627078-C-A |
| 146 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -4.55 | chr12-123627078-C-T |
| 146 | V→A | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.65) | -6.86 | ClinVar:1703884 |
| 146 | V→L | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.71) | -6.49 | ClinVar:2198556 |
| 146 | V→A | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.65) | -6.86 | COSV71194221 |
| 147 | Y→Y | synonymous_variant | gnomAD | — | 8.89e-06 | — | — | 0.00 | chr12-123627073-G-A |
| 147 | Y→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123627073-G-T |
| 147 | Y→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2126425 |
| 147 | Y→Y | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3607656 |
| 148 | V→V | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627070-G-A |
| 148 | V→I | missense_variant | gnomAD | — | 9.58e-06 | — | likely_benign (0.08) | -2.99 | chr12-123627072-C-T |
| 148 | V→I | missense_variant | ClinVar | Likely benign | — | — | likely_benign (0.08) | -2.99 | ClinVar:2604486 |
| 148 | V→I | missense_variant | COSMIC | — | — | — | likely_benign (0.08) | -2.99 | COSV107522311 |
| 149 | T→P | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.79) | -7.84 | ClinVar:3274962 |
| 150 | E→D | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.72) | -6.18 | chr12-123627064-C-G |
| 150 | E→E | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123627064-C-T |
| 150 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123627066-CTG-C |
| 150 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2765961 |
| 150 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2898481 |
| 151 | S→* | stop_gained | gnomAD | — | 4.10e-06 | LoF | — | — | chr12-123627062-G-C |
| 151 | S→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -3.59 | chr12-123627063-A-C |
| 151 | — | frameshift_variant | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:2835749 |
| 152 | Q→Q | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123627058-C-T |
| 152 | Q→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.71) | -5.71 | chr12-123627059-T-G |
| 152 | Q→Q | synonymous_variant | ClinVar | Uncertain significance | — | — | — | 0.00 | ClinVar:883543 |
| 153 | P→H | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.91) | -8.12 | COSV101424581 |
| 154 | D→H | missense_variant | gnomAD | — | 1.09e-05 | damaging | likely_pathogenic (0.86) | -6.56 | chr12-123627054-C-G |
| 155 | L→F | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.09) | -2.35 | chr12-123627049-C-A |
| 155 | L→F | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -2.35 | chr12-123627049-C-G |
| 155 | L→W | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.16) | -4.52 | chr12-123627050-A-C |
| 155 | L→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -2.87 | chr12-123627051-A-C |
| 155 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627051-A-G |
| 155 | L→M | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | -1.09 | chr12-123627051-A-T |
| 156 | S→S | synonymous_variant | gnomAD | — | 2.12e-05 | — | — | 0.00 | chr12-123627046-T-C |
| 156 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1570253 |
| 157 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -9.75 | chr12-123627044-C-A |
| 158 | K→N | missense_variant | gnomAD | — | 2.19e-05 | — | ambiguous (0.37) | -3.54 | chr12-123626490-C-A |
| 158 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123626492-TACTG-T |
| 160 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123626485-AT-A |
| 161 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626481-G-T |
| 161 | A→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -11.39 | chr12-123626483-C-G |
| 161 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.20) | -4.33 | chr12-123626483-C-T |
| 161 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -2.91 | COSV71194576 |
| 161 | A→T | missense_variant | COSMIC | — | — | — | likely_benign (0.20) | -4.33 | COSV109442771 |
| 162 | K→R | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | -3.06 | chr12-123626479-T-C |
| 162 | K→E | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | -1.34 | chr12-123626480-T-C |
| 163 | A→A | synonymous_variant | gnomAD | — | 1.78e-05 | — | — | 0.00 | chr12-123626475-G-A |
| 163 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2961832 |
| 164 | L→P | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (0.99) | -10.50 | chr12-123626473-A-G |
| 164 | L→F | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.72) | -8.12 | chr12-123626474-G-A |
| 164 | L→V | missense_variant | gnomAD | — | 4.10e-06 | — | ambiguous (0.40) | -7.31 | chr12-123626474-G-C |
| 164 | L→V | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.40) | -7.31 | ClinVar:3087894 |
| 164 | L→P | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -10.50 | ClinVar:3779607 |
| 164 | L→R | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.98) | -10.75 | COSV71194199 |
| 166 | H→H | synonymous_variant | gnomAD | — | 1.23e-05 | — | — | 0.00 | chr12-123626466-G-A |
| 166 | H→H | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1982698 |
| 166 | H→H | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV105350625 |
| 167 | L→F | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.15) | -4.68 | chr12-123626465-G-A |
| 167 | L→V | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.14) | -6.18 | chr12-123626465-G-C |
| 167 | L→F | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.15) | -4.68 | ClinVar:3087895 |
| 168 | N→N | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123626460-G-A |
| 168 | N→S | missense_variant | gnomAD | — | 6.84e-06 | — | likely_benign (0.08) | -3.36 | chr12-123626461-T-C |
| 168 | N→S | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.08) | -3.36 | ClinVar:3274960 |
| 169 | V→V | synonymous_variant | gnomAD | — | 3.42e-06 | — | — | 0.00 | chr12-123626457-G-A |
| 169 | V→F | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.62) | -9.53 | chr12-123626459-C-A |
| 169 | V→I | missense_variant | gnomAD | — | 2.94e-05 | — | likely_benign (0.07) | -0.68 | chr12-123626459-C-T |
| 169 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.07) | -0.68 | ClinVar:2182346 |
| 171 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123626453-CAG-C |
| 171 | V→D | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.94) | -12.23 | ClinVar:915406 |
| 171 | — | frameshift_variant | ClinVar | Likely pathogenic | — | LoF | — | — | ClinVar:3382064 |
| 172 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626448-A-G |
| 172 | T→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.24) | -5.38 | chr12-123626449-G-C |
| 172 | T→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.24) | -5.38 | chr12-123626450-T-A |
| 172 | T→S | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.24) | -5.38 | ClinVar:3274961 |
| 173 | V→M | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.15) | -2.46 | chr12-123626447-C-T |
| 174 | V→V | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123626442-C-T |
| 174 | V→L | missense_variant | gnomAD | — | 5.47e-06 | — | ambiguous (0.37) | -4.80 | chr12-123626444-C-G |
| 174 | V→M | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.49) | -5.64 | chr12-123626444-C-T |
| 174 | V→L | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.37) | -4.80 | ClinVar:2178158 |
| 174 | V→M | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.49) | -5.64 | ClinVar:1977645 |
| 174 | V→L | missense_variant | COSMIC | — | — | — | ambiguous (0.37) | -4.80 | COSV71194730 |
| 175 | L→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.26) | -4.84 | ClinVar:4618336 |
| 176 | D→G | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -10.00 | chr12-123626437-T-C |
| 177 | A→A | synonymous_variant | gnomAD | — | 1.04e-04 | — | — | 0.00 | chr12-123626433-A-G |
| 177 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626433-A-T |
| 177 | A→T | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.24) | -5.07 | chr12-123626435-C-T |
| 177 | A→A | synonymous_variant | ClinVar | Conflicting classifications of pathogenicity | — | — | — | 0.00 | ClinVar:882754 |
| 177 | A→A | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV107522313 |
| 177 | A→T | missense_variant | COSMIC | — | — | — | likely_benign (0.24) | -5.07 | COSV71194288 |
| 178 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626430-A-T |
| 178 | A→T | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.60) | -6.18 | chr12-123626432-C-T |
| 179 | V→V | synonymous_variant | gnomAD | — | 1.71e-05 | — | — | 0.00 | chr12-123626427-G-A |
| 179 | V→V | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123626427-G-T |
| 179 | V→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.19) | -5.82 | chr12-123626428-A-G |
| 179 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.12) | -4.13 | chr12-123626429-C-T |
| 179 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123626429-CAGCAGCATCT-C |
| 179 | V→F | missense_variant | ClinVar | Pathogenic | — | damaging | likely_pathogenic (0.72) | -10.04 | ClinVar:217277 |
| 179 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2977464 |
| 179 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2983669 |
| 180 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624862-G-A |
| 180 | G→D | missense_variant | gnomAD | — | 1.09e-05 | damaging | likely_pathogenic (0.98) | -8.24 | chr12-123626425-C-T |
| 180 | G→S | missense_variant | gnomAD | — | 1.57e-05 | — | likely_benign (0.29) | -5.30 | chr12-123626426-C-T |
| 180 | G→D | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.98) | -8.24 | ClinVar:977417 |
| 181 | Y→C | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.32) | -6.33 | chr12-123624860-T-C |
| 182 | I→V | missense_variant | gnomAD | — | 5.47e-06 | — | likely_benign (0.07) | -2.25 | chr12-123624858-T-C |
| 183 | M→I | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.59) | -3.88 | chr12-123624853-C-T |
| 183 | M→T | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.72) | -6.03 | chr12-123624854-A-G |
| 184 | E→D | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.49) | -4.36 | chr12-123624850-C-G |
| 184 | E→* | stop_gained | ClinVar | — | — | LoF | — | — | ClinVar:4381676 |
| 184 | E→* | stop_gained | COSMIC | — | — | LoF | — | — | COSV99434892 |
| 185 | K→K | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624847-T-C |
| 185 | K→R | missense_variant | gnomAD | — | 1.44e-05 | — | likely_benign (0.10) | -4.16 | chr12-123624848-T-C |
| 185 | K→E | missense_variant | gnomAD | — | 7.53e-06 | — | likely_benign (0.31) | -6.94 | chr12-123624849-T-C |
| 185 | K→E | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.31) | -6.94 | ClinVar:1432529 |
| 185 | K→K | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2744942 |
| 186 | A→E | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.88) | -6.34 | chr12-123624845-G-T |
| 187 | D→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.68) | -6.23 | chr12-123624843-C-G |
| 187 | D→N | missense_variant | gnomAD | — | 1.51e-05 | — | likely_benign (0.25) | -4.95 | chr12-123624843-C-T |
| 189 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624835-G-T |
| 189 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.12) | -4.26 | chr12-123624837-C-T |
| 189 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -4.26 | ClinVar:1696202 |
| 189 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2839826 |
| 190 | I→T | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.85) | -8.33 | chr12-123624833-A-G |
| 190 | I→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | -2.57 | chr12-123624834-T-A |
| 191 | V→V | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123624829-A-G |
| 191 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.19) | -5.40 | chr12-123624831-C-T |
| 191 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2997166 |
| 192 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -11.00 | chr12-123624827-C-A |
| 192 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123624828-C-CA |
| 192 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:1416368 |
| 193 | A→G | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.57) | -6.99 | chr12-123624824-G-C |
| 193 | — | frameshift_variant | gnomAD | — | 8.89e-06 | LoF | — | — | chr12-123624824-GCA-G |
| 193 | — | frameshift_variant | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:1176971 |
| 195 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624817-T-A |
| 195 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.92) | -7.68 | chr12-123624818-C-A |
| 195 | G→R | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (1.00) | -8.93 | chr12-123624819-C-T |
| 197 | V→A | missense_variant | gnomAD | — | 7.53e-06 | — | ambiguous (0.41) | -5.17 | chr12-123624812-A-G |
| 197 | V→F | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.87) | -9.11 | chr12-123624813-C-A |
| 197 | V→A | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.41) | -5.17 | ClinVar:1373531 |
| 199 | N→N | synonymous_variant | gnomAD | — | 7.66e-05 | — | — | 0.00 | chr12-123624805-G-A |
| 199 | N→N | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:715309 |
| 199 | N→S | missense_variant | COSMIC | — | — | — | likely_benign (0.11) | 3.07 | COSV99434254 |
| 200 | G→R | missense_variant | gnomAD | — | 1.64e-05 | damaging | likely_pathogenic (0.99) | -10.12 | chr12-123624804-C-T |
| 200 | G→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -10.12 | ClinVar:1981639 |
| 201 | G→G | synonymous_variant | gnomAD | — | 7.53e-06 | — | — | 0.00 | chr12-123624799-T-G |
| 201 | G→G | synonymous_variant | ClinVar | Uncertain significance | — | — | — | 0.00 | ClinVar:882753 |
| 202 | I→I | synonymous_variant | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123624796-A-G |
| 202 | I→S | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.98) | -9.38 | chr12-123624797-A-C |
| 202 | I→T | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.97) | -6.29 | chr12-123624797-A-G |
| 202 | — | inframe_deletion | ClinVar | Pathogenic | — | — | — | — | ClinVar:217280 |
| 202 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3010734 |
| 203 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624793-A-G |
| 203 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624793-A-T |
| 203 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:740083 |
| 203 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3700710 |
| 204 | N→Y | missense_variant | gnomAD | — | 1.64e-05 | damaging | likely_pathogenic (0.98) | -11.44 | chr12-123624792-T-A |
| 204 | N→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.87) | -9.81 | chr12-123624792-T-G |
| 204 | N→Y | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.98) | -11.44 | ClinVar:4124 |
| 205 | K→N | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.95) | -6.80 | chr12-123624787-C-G |
| 205 | K→N | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.95) | -6.80 | ClinVar:982930 |
| 206 | I→M | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.30) | -4.94 | chr12-123622759-A-C |
| 206 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622759-A-G |
| 207 | G→V | missense_variant | gnomAD | — | 2.26e-05 | damaging | likely_pathogenic (1.00) | -10.19 | chr12-123622757-C-A |
| 207 | G→R | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -10.31 | chr12-123622758-C-T |
| 208 | T→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -8.87 | chr12-123622754-G-A |
| 208 | T→N | missense_variant | gnomAD | — | 4.11e-06 | damaging | likely_pathogenic (0.94) | -10.37 | chr12-123622754-G-T |
| 208 | T→N | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.94) | -10.37 | ClinVar:2537812 |
| 209 | N→S | missense_variant | gnomAD | — | 1.92e-05 | — | likely_benign (0.08) | -1.97 | chr12-123622751-T-C |
| 212 | A→T | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.95) | -8.56 | chr12-123622743-C-T |
| 212 | A→T | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.95) | -8.56 | COSV108044470 |
| 212 | A→S | missense_variant | COSMIC | — | — | — | ambiguous (0.45) | -6.56 | COSV53017684 |
| 213 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622738-C-T |
| 213 | V→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -4.62 | chr12-123622740-C-A |
| 213 | V→M | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.15) | -5.55 | chr12-123622740-C-T |
| 213 | V→L | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.14) | -4.62 | ClinVar:3274963 |
| 214 | C→C | synonymous_variant | gnomAD | — | 1.85e-05 | — | — | 0.00 | chr12-123622735-A-G |
| 214 | C→Y | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.80) | -6.59 | chr12-123622736-C-T |
| 214 | C→R | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.96) | -10.68 | chr12-123622737-A-G |
| 214 | C→C | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2889787 |
| 215 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123622733-GCA-G |
| 215 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2829720 |
| 216 | K→N | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.76) | -6.16 | chr12-123622729-T-G |
| 216 | K→T | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.55) | -7.00 | chr12-123622730-T-G |
| 217 | A→V | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.12) | -3.78 | chr12-123622727-G-A |
| 217 | A→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -3.78 | ClinVar:1043126 |
| 218 | Q→Q | synonymous_variant | gnomAD | — | 1.16e-05 | — | — | 0.00 | chr12-123622723-C-T |
| 218 | Q→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -3.98 | chr12-123622724-T-C |
| 218 | Q→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622725-G-A |
| 218 | Q→K | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.17) | -4.77 | chr12-123622725-G-T |
| 218 | Q→Q | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2570853 |
| 219 | N→N | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123622720-G-A |
| 220 | K→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.16) | -4.99 | chr12-123622718-T-C |
| 220 | K→R | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.16) | -4.99 | ClinVar:882752 |
| 221 | P→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.73) | -6.70 | chr12-123622715-G-A |
| 222 | F→F | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622711-G-A |
| 222 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.85) | -4.93 | chr12-123622713-A-G |
| 222 | F→L | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.85) | -4.93 | COSV108044475 |
| 223 | — | inframe_deletion | gnomAD | — | 6.84e-07 | — | — | — | chr12-123622708-ATAGAAAGGT-A |
| 223 | Y→C | missense_variant | gnomAD | — | 1.30e-05 | damaging | ambiguous (0.54) | -7.75 | chr12-123622709-T-C |
| 223 | Y→C | missense_variant | ClinVar | Uncertain significance | — | damaging | ambiguous (0.54) | -7.75 | ClinVar:1906761 |
| 224 | V→V | synonymous_variant | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123622705-C-T |
| 224 | V→A | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.43) | -5.68 | chr12-123622706-A-G |
| 224 | V→M | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.94) | -9.12 | chr12-123622707-C-T |
| 225 | V→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.26) | -5.42 | chr12-123622703-A-G |
| 226 | A→V | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.41) | -5.81 | chr12-123622700-G-A |
| 226 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.18) | -4.00 | chr12-123622701-C-T |
| 227 | E→E | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123622696-T-C |
| 227 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622697-TC-T |
| 227 | E→K | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -10.44 | chr12-123622698-C-T |
| 228 | S→S | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622693-A-G |
| 228 | S→N | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.92) | -8.19 | chr12-123622694-C-T |
| 228 | — | frameshift_variant | gnomAD | — | 4.10e-06 | LoF | — | — | chr12-123622694-CTT-C |
| 228 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2762330 |
| 229 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -5.68 | chr12-123622692-A-G |
| 229 | F→F | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53015462 |
| 230 | K→N | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.99) | -9.12 | chr12-123622687-C-G |
| 230 | K→K | synonymous_variant | gnomAD | — | 7.52e-06 | — | — | 0.00 | chr12-123622687-C-T |
| 230 | K→M | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.99) | -9.87 | COSV53017385 |
| 231 | F→L | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (1.00) | -9.00 | chr12-123622686-A-G |
| 232 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622683-CAAACTTG-C |
| 232 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2765937 |
| 233 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622678-C-G |
| 233 | R→Q | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.81) | -7.75 | chr12-123622679-C-T |
| 233 | R→W | missense_variant | gnomAD | — | 4.79e-06 | damaging | likely_pathogenic (0.92) | -9.75 | chr12-123622680-G-A |
| 233 | R→W | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.92) | -9.75 | COSV53016012 |
| 234 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622675-G-C |
| 234 | L→P | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.97) | -9.96 | chr12-123622676-A-G |
| 234 | L→L | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV99434759 |
| 234 | L→P | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.97) | -9.96 | COSV53015966 |
| 234 | L→F | missense_variant | COSMIC | — | — | — | likely_benign (0.34) | -6.12 | COSV99434394 |
| 235 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (1.00) | -7.96 | chr12-123622672-A-C |
| 235 | F→V | missense_variant | ClinVar | Pathogenic | — | damaging | likely_pathogenic (0.97) | -9.65 | ClinVar:217282 |
| 235 | F→F | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2781763 |
| 236 | P→R | missense_variant | gnomAD | — | 4.79e-06 | damaging | likely_pathogenic (0.99) | -12.31 | chr12-123622670-G-C |
| 236 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:1461865 |
| 237 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123622666-T-G |
| 237 | L→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.62) | -7.44 | chr12-123622668-G-C |
| 237 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2829479 |
| 238 | N→N | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622663-G-A |
| 238 | N→K | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (0.79) | -6.92 | chr12-123622663-G-C |
| 238 | N→S | missense_variant | gnomAD | — | 2.05e-06 | — | likely_benign (0.11) | -4.32 | chr12-123622664-T-C |
| 238 | N→N | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2693620 |
| 239 | Q→Q | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123622660-C-T |
| 239 | Q→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622662-G-A |
| 240 | Q→E | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.09) | -4.50 | chr12-123622659-G-C |
| 241 | D→D | synonymous_variant | gnomAD | — | 9.58e-06 | — | — | 0.00 | chr12-123622654-G-A |
| 241 | D→D | synonymous_variant | ClinVar | Conflicting classifications of pathogenicity | — | — | — | 0.00 | ClinVar:198774 |
| 242 | V→I | missense_variant | gnomAD | — | 3.35e-05 | — | likely_benign (0.09) | -2.43 | chr12-123622653-C-T |
| 242 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.09) | -2.43 | ClinVar:2342295 |
| 242 | V→V | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV106362880 |
| 244 | D→G | missense_variant | gnomAD | — | 7.53e-06 | — | likely_benign (0.16) | -3.91 | chr12-123622646-T-C |
| 247 | K→R | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.17) | -3.94 | ClinVar:2584983 |
| 247 | K→N | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.99) | -6.51 | COSV104586314 |
| 248 | Y→* | stop_gained | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123621918-A-C |
| 248 | Y→C | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.81) | -4.74 | chr12-123621919-T-C |
| 249 | K→E | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.31) | -5.13 | chr12-123621917-T-C |
| 250 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -2.46 | ClinVar:4017109 |
| 251 | D→D | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621909-G-A |
| 251 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2892296 |
| 251 | D→Y | missense_variant | COSMIC | — | — | — | likely_benign (0.20) | -4.08 | COSV53016683 |
| 253 | L→L | synonymous_variant | gnomAD | — | 8.55e-05 | — | — | 0.00 | chr12-123621903-G-A |
| 253 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621903-G-C |
| 253 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3013246 |
| 254 | K→K | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621900-C-T |
| 254 | K→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | -2.24 | chr12-123621901-T-C |
| 254 | — | frameshift_variant | gnomAD | — | 6.16e-06 | LoF | — | — | chr12-123621902-TGA-T |
| 254 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:1683289 |
| 255 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621897-G-A |
| 255 | V→V | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621897-G-C |
| 255 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1616596 |
| 255 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2787901 |
| 256 | A→A | synonymous_variant | gnomAD | — | 2.67e-05 | — | — | 0.00 | chr12-123621894-C-T |
| 256 | A→V | missense_variant | gnomAD | — | 1.71e-05 | — | likely_benign (0.08) | -1.77 | chr12-123621895-G-A |
| 256 | — | frameshift_variant | gnomAD | — | 7.53e-06 | LoF | — | — | chr12-123621896-C-CGACCT |
| 256 | A→T | missense_variant | gnomAD | — | 8.62e-05 | — | likely_benign (0.07) | -1.92 | chr12-123621896-C-T |
| 256 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:762889 |
| 256 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.07) | -1.92 | ClinVar:1524276 |
| 256 | A→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.08) | -1.77 | ClinVar:2140196 |
| 256 | — | frameshift_variant | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:2891124 |
| 256 | A→A | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53016619 |
| 256 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.08) | -1.77 | COSV53015723 |
| 256 | A→S | missense_variant | COSMIC | — | — | — | likely_benign (0.07) | -2.48 | COSV99434053 |
| 257 | Q→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123621893-G-A |
| 257 | Q→E | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.06) | -1.95 | chr12-123621893-G-C |
| 257 | Q→K | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.06) | 0.23 | chr12-123621893-G-T |
| 258 | T→T | synonymous_variant | gnomAD | — | 1.09e-05 | — | — | 0.00 | chr12-123621888-A-G |
| 258 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2984521 |
| 259 | G→V | missense_variant | COSMIC | — | — | — | likely_benign (0.12) | -4.64 | COSV53017342 |
| 261 | D→A | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.13) | -4.20 | chr12-123621880-T-G |
| 261 | D→N | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | -0.44 | chr12-123621881-C-T |
| 262 | L→I | missense_variant | COSMIC | — | — | — | likely_benign (0.12) | -5.25 | COSV99434871 |
| 263 | K→K | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621873-T-C |
| 263 | K→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | 2.47 | chr12-123621874-T-C |
| 263 | K→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | 0.98 | chr12-123621874-T-G |
| 263 | K→Q | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.09) | -0.44 | chr12-123621875-T-G |
| 264 | E→E | synonymous_variant | gnomAD | — | 8.21e-06 | — | — | 0.00 | chr12-123621870-C-T |
| 264 | E→Q | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -1.53 | chr12-123621872-C-G |
| 264 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123621872-CTT-C |
| 264 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2898199 |
| 264 | E→Q | missense_variant | COSMIC | — | — | — | likely_benign (0.09) | -1.53 | COSV99434770 |
| 265 | E→E | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621867-C-T |
| 265 | E→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -4.85 | chr12-123621868-T-C |
| 265 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2824669 |
| 266 | H→H | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123621864-A-G |
| 266 | H→Y | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.55) | -5.26 | chr12-123621866-G-A |
| 266 | H→D | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.78) | -8.23 | chr12-123621866-G-C |
| 267 | P→P | synonymous_variant | gnomAD | — | 2.05e-05 | — | — | 0.00 | chr12-123621861-C-T |
| 267 | P→L | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.88) | -6.53 | chr12-123621862-G-A |
| 267 | P→P | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:738949 |
| 267 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2769348 |
| 267 | P→P | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53016848 |
| 268 | W→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:4700314 |
| 269 | V→V | synonymous_variant | gnomAD | — | 3.15e-05 | — | — | 0.00 | chr12-123621855-G-A |
| 269 | V→V | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123621855-G-C |
| 269 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1667617 |
| 269 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.13) | 1.34 | ClinVar:1906251 |
| 269 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1917279 |
| 269 | V→V | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53017155 |
| 270 | D→N | missense_variant | gnomAD | — | 8.89e-06 | damaging | likely_pathogenic (0.98) | -9.50 | chr12-123621854-C-T |
| 270 | D→H | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (1.00) | -12.12 | ClinVar:1465208 |
| 270 | D→D | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53016416 |
| 271 | Y→Y | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621849-G-A |
| 271 | Y→C | missense_variant | gnomAD | — | 3.56e-05 | damaging | likely_pathogenic (0.87) | -7.33 | chr12-123621850-T-C |
| 271 | Y→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.96) | -6.68 | chr12-123621851-A-G |
| 271 | Y→C | missense_variant | ClinVar | Pathogenic/Likely pathogenic | — | damaging | likely_pathogenic (0.87) | -7.33 | ClinVar:217281 |
| 271 | Y→F | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.20) | -5.05 | ClinVar:4740486 |
| 272 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2719607 |
| 273 | A→P | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | 0.39 | chr12-123621845-C-G |
| 274 | P→R | missense_variant | ClinVar | Pathogenic | — | damaging | likely_pathogenic (0.96) | -11.12 | ClinVar:217278 |
| 274 | P→A | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.43) | -6.02 | ClinVar:4017107 |
| 274 | P→A | missense_variant | COSMIC | — | — | — | ambiguous (0.43) | -6.02 | COSV99434579 |
| 275 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2823944 |
| 276 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123621834-TAAGG-T |
| 276 | L→V | missense_variant | gnomAD | — | 1.03e-05 | damaging | likely_benign (0.30) | -7.73 | chr12-123621836-A-C |
| 277 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621831-G-A |
| 277 | — | frameshift_variant | gnomAD | — | 2.05e-06 | LoF | — | — | chr12-123621832-AT-A |
| 277 | I→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.17) | -5.24 | chr12-123621833-T-C |
| 278 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621828-A-G |
| 278 | T→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.95) | -8.38 | chr12-123621829-G-A |
| 278 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123621829-G-GTGAT |
| 279 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621827-G-A |
| 279 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2797947 |
| 280 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621822-C-G |
| 280 | L→L | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123621822-C-T |
| 280 | L→Q | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.97) | -10.62 | chr12-123621823-A-T |
| 280 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2801144 |
| 281 | F→F | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123621819-A-G |
| 281 | — | inframe_deletion | gnomAD | — | 6.84e-07 | — | — | — | chr12-123621821-ACAG-A |
| 282 | T→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (1.00) | -8.87 | chr12-123621817-G-A |
| 282 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123621818-TA-T |
| 283 | D→G | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.99) | -10.12 | chr12-123621814-T-C |
| 283 | D→G | missense_variant | ClinVar | Conflicting classifications of pathogenicity | — | damaging | likely_pathogenic (0.99) | -10.12 | ClinVar:1426819 |
| 285 | G→G | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123621807-G-A |
| 285 | G→G | synonymous_variant | gnomAD | — | 1.71e-05 | — | — | 0.00 | chr12-123621807-G-C |
| 285 | G→S | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.92) | -8.87 | chr12-123621809-C-T |
| 285 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2643513 |
| 285 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2981686 |
| 285 | G→D | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.98) | -9.12 | COSV53016088 |
| 286 | V→M | missense_variant | gnomAD | — | 1.37e-05 | damaging | likely_pathogenic (0.64) | -6.99 | chr12-123621806-C-T |
| 286 | V→M | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.64) | -6.99 | ClinVar:307528 |
| 286 | V→A | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.69) | -5.52 | ClinVar:2130873 |
| 286 | V→M | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.64) | -6.99 | COSV53016408 |
| 287 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621801-C-A |
| 287 | L→L | synonymous_variant | gnomAD | — | 1.64e-05 | — | — | 0.00 | chr12-123621801-C-T |
| 287 | L→R | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.94) | -9.66 | chr12-123621802-A-C |
| 287 | L→P | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.99) | -9.79 | chr12-123621802-A-G |
| 287 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2992127 |
| 288 | T→I | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.92) | -7.30 | chr12-123621799-G-A |
| 288 | T→R | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.90) | -9.49 | chr12-123621799-G-C |
| 288 | T→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.90) | -9.49 | ClinVar:2584935 |
| 289 | P→S | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.82) | -6.94 | chr12-123621797-G-A |
| 290 | S→S | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621792-T-C |
| 291 | A→A | synonymous_variant | gnomAD | — | 4.11e-06 | — | — | 0.00 | chr12-123621789-T-G |
| 291 | A→T | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.85) | -7.55 | chr12-123621791-C-T |
| 291 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1910644 |
| 292 | V→I | missense_variant | COSMIC | — | — | — | likely_benign (0.15) | -6.97 | COSV53018031 |
| 293 | S→S | synonymous_variant | gnomAD | — | 1.40e-04 | — | — | 0.00 | chr12-123621783-G-A |
| 293 | S→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.34) | -7.31 | chr12-123621785-T-C |
| 293 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:732578 |
| 293 | S→G | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.34) | -7.31 | ClinVar:4247692 |
| 293 | S→S | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV99434724 |
| 294 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2105244 |
| 295 | E→D | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.97) | -8.62 | chr12-123621777-C-G |
| 295 | E→G | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.95) | -8.37 | chr12-123621778-T-C |
| 295 | E→D | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.97) | -8.62 | ClinVar:1509586 |
| 296 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621774-G-A |
| 296 | L→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.86) | -8.62 | chr12-123621776-G-C |
| 296 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2969477 |
| 297 | I→L | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.46) | -6.90 | chr12-123621773-T-G |
| 297 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1579754 |
| 298 | — | inframe_deletion | gnomAD | — | 6.84e-07 | — | — | — | chr12-123621769-TTGA-T |
| 299 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621765-G-A |
| 299 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621765-G-C |
| 299 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2736177 |
| 299 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2844897 |
| 299 | L→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.72) | -6.56 | COSV105107975 |
| 300 | Y→C | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.90) | -7.87 | chr12-123621763-T-C |
| 300 | Y→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.89) | -7.28 | chr12-123621764-A-G |
| 301 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621759-C-A |
| 301 | L→M | missense_variant | COSMIC | — | — | — | likely_benign (0.26) | -3.50 | COSV99434855 |
| 301 | L→L | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53017328 |
747 variants in the shared canonical core.
LoF = frameshift / stop-gain / splice-disrupting — inherently loss-of-function, flagged by consequence (AlphaMissense and ESM-C score only missense/substitutions, so they are blank here by design, not by absence of impact). AlphaMissense is computed in the canonical reading frame, so it scores the shared core but reads N/A across an isoform-unique extension — use ESM-C ΔLLR there.