UBE2M · ENST00000253023.8

EXTENDED 248 aa (canonical 183 aa) · UniProt P61081 · CDLMPS

chr19:58558576:-:ACG:ENST00000253023.8

AI summary N-terminal extension adds a disordered, Gly/Ala-rich tail with one loosely-docked helix, but no domain, localization, or biophysical change to the UBE2M core.

How it diverges

The added 65-residue N-terminus folds moderately well in isolation (mean pLDDT 0.79) and contains one qualifying helix, but that helix shows weak, diffuse contacts and high PAE (~12-19 Å) against the shared catalytic core, meaning its orientation relative to the retained E2 domain is essentially unresolved rather than a stably integrated new structural module. DeepLoc, SignalP/TargetP, InterPro domains, and whole-protein biophysics all read unchanged versus canonical, so no mechanism finding here contradicts or extends the known nuclear/cytosolic, cullin-neddylating function.

Why it matters

UBE2M's activity depends on its UBC catalytic core (charged by the NEDD8 E1, engaged by DCN1 via a short N-terminal peptide, catalyzing via C111) and on nuclear/cytosolic access to cullin-RING ligases. Because the shared core is structurally unperturbed (low RMSD, high shared pLDDT/pTM) and no domain, compartment, or biophysical shift accompanies the extension, this isoform's added tail does not appear to alter catalytic core integrity, subcellular distribution, or the DCN1-binding surface as currently modeled; its loosely-docked helix is a structural curiosity without demonstrated functional consequence for cullin neddylation or the described non-cullin substrate interactions.

LLM confidence low

Extension is real (multi-cell-line detection, MS-validated peptides, strong conservation/phyloP) but germline-constraint and disease-variant metrics are uninterpretable/depleted for this never-coding-turned-coding region, and the one candidate structural feature (helix) has high inter-region PAE, so no tier-2 mechanism passes the confidence bar for tagging.

Folding

Canonical (183 aa)

Download CIF

Isoform (248 aa)

Download CIF

Coloured by ESMFold2 pLDDT confidence (blue = high, orange/red = low). Differential region — residues 1–65 (added in isoform) — 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 (1–65).

Evidence — click any tile for the differential-region detail

C Conservation Interesting

LLM reasoning

The N-terminal extension added by this isoform shows strong, convergent evidence of purifying selection rather than being an inert byproduct of upstream UTR/intron sequence. Amino-acid identity across primates is high (95.5%) and remains substantial across mammals (85.1%), though both trail the canonical protein's near-invariant identity (99.96% primates, 98.6% mammals) — consistent with an added region under real but somewhat weaker constraint than the ancient core. Absolute phyloP over the unique region is 4.01, well above the ~2 threshold for strong constraint, indicating base-level purifying selection independent of the reading-frame metrics. frac_intact values (0.25 primates, 0.17 mammals) are not read as a conservation gap given the short span confound. Together these three signals converge on the same conclusion: this extension is evolutionarily conserved and likely functionally real, not just extended translation into previously noncoding sequence.

Unique region 95.5% similar across primates

Conservation metric	Canonical ORF	Differential ORF
Mean AA identity	100%	96%
Frame intact (fraction of species)	84%	25%
Species aligned	25	24
Species frame-intact	21	6
Start codon conserved	96%	91%
Deepest intact species	Microcebus_murinus	Callithrix_jacchus
Phylo depth (MRCA)	7	6

Unique region 85.1% similar across mammals

Conservation metric	Canonical ORF	Differential ORF
Mean AA identity	99%	85%
Frame intact (fraction of species)	65%	17%
Species aligned	20	18
Species frame-intact	13	3
Start codon conserved	100%	92%
Deepest intact species	Echinops_telfairi	Bos_taurus
Phylo depth (MRCA)	12	11

Unique region PhyloP: 4.01 — purifying selection

Track	Differential	Shared	vs shared
phyloP mean	4.01	5.63	0.713
phastCons mean	0.322	0.897	—

Property	Canonical	Isoform
Start codon	ATG	ACG
Kozak context (−9..+4)	GGCGGCAGGATGA	AGCCGGACTACGG
phyloP at start codon	6.16	6.44
phastCons at start codon	1	0.208
phyloP over Kozak window	6.63	4.56
phastCons over Kozak window	1	0.0758
Kozak mismatch — full consensus	5	7
Kozak window GC content	0.692	0.692

D Detection Interesting

LLM reasoning

This alternative N-terminal extension is robustly detected at every level: ribosome-profiling initiation is seen reproducibly across all 6 cell lines tested, start-site usage is efficient (max initiation efficiency 0.119, comparable to and in some lines within the same order of magnitude as the canonical start's efficiency, e.g. 0.107 vs 0.152 in K562), and critically, mass spectrometry independently validates 5 of 14 isoform-unique tryptic peptides spanning the added N-terminal segment (positions 0-65 of the differential region), with strong PepQuery2 scores (hyperscores up to 57.6, p-values down to ~1e-4). The convergence of transcriptional/translational initiation evidence with direct peptide-level proteomic confirmation of the unique region is strong, multi-modal support that this extended isoform is a real, actively translated and stably expressed protein product rather than a rare or spurious translation event.

detected in 6/6 cell lines

Cell line	Canonical	Isoform	p-value
HeLa	—	10.6	0.000142
K562	7.03	4.94	2.61e-21
U2OS	0.81	1.18	1.37e-13
RPE1 Async	1.2	1.09	6.1e-05
RPE1 Que	0.811	0.316	1.2e-13
RPE1 Sen	1.13	1.09	5.15e-06

alt used 0.7× vs canonical

Cell line	Canonical	Isoform
HeLa	—	0.119
K562	0.152	0.107
U2OS	0.0303	0.0441
RPE1 Async	0.0233	0.0211
RPE1 Que	0.0281	0.0109
RPE1 Sen	0.0204	0.0196

5/14 isoform-unique peptides validated

Feature	Canonical	Isoform
Tryptic peptides (in-silico)	29	14
Validated by mass-spec	0	5
Isoform-unique peptides	—	14

L Localization Not interesting

LLM reasoning

Adding this 65-residue glycine/alanine-rich N-terminal extension does not alter predicted subcellular fate: DeepLoc calls both isoform and canonical as Cytoplasm (top probability 0.57 vs 0.56, a marginal shift), with identical retained nuclear localization signal and identical peripheral/soluble membrane association. Neither a secretory signal peptide nor a mitochondrial transit peptide is predicted for either form (both 'OTHER'/'noTP' with negligible probability deltas ~0.0003-0.0015), so no new targeting signal is introduced. Overall this dimension shows no evidence that the extension redirects or retargets the protein.

iso: Cytoplasm | canon: Cytoplasm

Property	Canonical	Isoform
Predicted location	Cytoplasm	Cytoplasm
Sorting signals	Nuclear localization signal	Nuclear localization signal
Membrane	Peripheral\|Soluble	Peripheral\|Soluble

iso: noTP | canon: noTP

Predictor	Canonical	Isoform
TargetP	noTP	noTP
SignalP	OTHER	OTHER

M Mutation Landscape Not interesting

LLM reasoning

Disease-variant density argues against a signal here: only 5 disease-annotated records fall in the unique region versus 113 in the shared core (enrichment ratio 0.12), zero of which are ClinVar pathogenic anywhere on the isoform, and the best COSMIC recurrence in the unique region is a single intronic-annotated variant with sample count 4 — far below the recurrent, AlphaMissense-pathogenic missense hits found in the shared/canonical region (e.g. Pro91His AM=0.9998, Lys36Asn AM=0.9954, Gly171Asp AM=0.9678). No start-lost variants were found at or near the alternative initiation codon. The germline-constraint member (gnomAD depletion, ESM-C) is uninterpretable by construction since this extension's unique region was never-coding 5'UTR/intron sequence, so it cannot be used to argue either way. With the one legitimately readable member (disease density) showing depletion rather than concentration, and no clustering or start-codon disruption to offset it, the evidence points to no meaningful disease signal in this isoform's differential region.

gnomAD variants 1.19× more in unique region — tolerant

Variant set	Differential	Shared	Depletion ratio
gnomAD variants	91	215	1.2×

Property	Differential	Shared	Enrichment
ESM-C mean LLR	-1.69	-0.0159	—
Constrained positions	0	0	—

Variant set	Differential	Shared	Enrichment
Scorable variants	71	209	0.96×
Damaging variants	4	54	0.21×
— of which loss-of-function	4	2	5.6×
AlphaMissense-pathogenic	0	30	0×

Property	Differential	Shared
Mean ΔLLR (ESM-C)	-1.45	-3.64
Min ΔLLR (ESM-C)	-5.89	-13.9
Mean AlphaMissense	—	0.419

Disease variants 8.03× less in unique region — depleted

Variant set	Differential	Shared	Enrichment
Disease variants	5	113	0.12×
Pathogenic	0	0	—

Variant set	Differential	Shared	Enrichment
Scorable variants	5	111	0.13×
Damaging variants	0	69	0×
— of which loss-of-function	0	13	0×
AlphaMissense-pathogenic	0	47	0×

Property	Differential	Shared
Mean ΔLLR (ESM-C)	-0.717	-7.34
Min ΔLLR (ESM-C)	-2.95	-14.4
Mean AlphaMissense	—	0.599

P Predicted Structure Neutral

LLM reasoning

The 65-residue N-terminal extension is modestly confident overall (mean pLDDT 0.787) and contains one qualifying 17-residue helix (residues 16-32, pLDDT 0.748), but this element is not convincingly integrated with the retained core: contacts are concentrated within the extension itself (residues 13-15, 33-34) with only scattered single contacts to the shared region, and the PAE between the helix and the shared core (residues 66-248) averages 11.65 Å with values up to ~30 Å, indicating the relative placement is largely unresolved. The shared core itself is unperturbed — RMSD 1.48 Å against a healthy shared pLDDT (0.87-0.90) and global pTM (0.77-0.84), so no real refolding signal there either. Overall this reads as a locally-folded but loosely-docked extension without a clear structural or functional signal in either direction.

pLDDT Differential Region: 0.787

Metric	Canonical	Isoform
pLDDT (whole protein)	0.869	0.873

Metric	Differential	Shared	Enrichment
pLDDT	0.787	0.751	1

Shared-Region RMSD: 1.48 Å

Property	Canonical	Isoform
Shared-region pLDDT	0.869	0.904

1 secondary structure identified in unique region

Metric	Differential	Shared
Alpha helices	1	4
Beta strands	0	2
Longest element (aa)	17	13
Mean pLDDT	0.75	0.96

Isoform-unique	Shared core
alpha helix 16–32 17 aa · pLDDT 0.75	alpha helix 94–105 12 aa · pLDDT 0.92
—	beta strand 125–131 7 aa · pLDDT 0.98
—	beta strand 139–147 9 aa · pLDDT 0.98
—	alpha helix 190–202 13 aa · pLDDT 0.91
—	alpha helix 212–219 8 aa · pLDDT 0.96
—	alpha helix 222–234 13 aa · pLDDT 0.97

Isoform-unique	Shared core
beta strand 2–9 8 aa · pLDDT 0.70	alpha helix 72–78 7 aa · pLDDT 0.56
beta strand 38–42 5 aa · pLDDT 0.88	beta strand 112–116 5 aa · pLDDT 0.93
beta strand 57–61 5 aa · pLDDT 0.85	—

S Structural Characteristics Neutral

LLM reasoning

No domain gain/loss and no strong whole-protein biophysical shift accompany this N-terminal extension, while the sparse-autoencoder magnitude check just clears threshold (11.54 vs 10.0), giving one weak positive signal against two negatives. The added 66-aa segment overlaps no real InterPro domain (only generic MobiDB-lite disorder calls), so no structural module is gained or lost. Whole-protein hydropathy, fraction-charged, and disorder deltas are all small (gravy -0.012, fraction-charged -0.021, disorder +0.029), none reaching a distinct shift despite the unique region itself being highly disordered, low-complexity, and prion-like relative to the shared core — these regional biases are diluted at the whole-protein level. The sparse-autoencoder shift barely passes its magnitude threshold, and gained/lost feature counts (158 vs 36) are not informative on their own. Overall the evidence is mixed and none of it strongly argues the extension changes protein structural character in a decisive way.

No diverging domains

Feature	Canonical	Isoform
InterPro domains	10	10
Short linear motifs	2	2

similar hydropathy · less charged (-0.08) · more disordered (+0.11)

Property	Differential	Shared	Enrichment
Isoelectric point (pI)	12	7.59	1.58
Hydropathy (GRAVY)	-0.565	-0.517	1.09
Fraction charged	0.2	0.279	0.718
Disorder fraction	0.221	0.108	2.04
Disorder-promoting	0.954	0.541	1.76
Low-complexity fraction	0.969	0	—
Prion-like fraction	0.446	0.284	1.57
LLPS score	0.386	0.159	2.43
π–π propensity	0.139	0.262	0.528
Aromaticity	0	0.0984	0
Instability index	44	40.5	1.09
Shannon entropy	2.53	4.11	0.616
Normalized complexity	0.586	0.952	0.616

194 SAE features differ

Feature	Label	Description	Activation	Prevalence
#448	N-terminal leader/targeting segments	N-terminal leader/targeting segments: the feature activates on the extreme N-terminus (first 2–5 residues) of proteins, especially the N-region of signal peptides and organelle transit peptides, and more generally on short, disordered/low-complexity N-terminal tails; strongest at residue ~3 and largely independent of amino-acid identity, occurring across all taxa and functions.	13.58	2
#15545	Low-complexity disordered regions	Intrinsic disorder/low-complexity segments enriched in small, polar and charged residues (S/T/N/G/A/E/D/R/K), especially N-terminal tails, C-terminal tails, and inter-domain regions that contain short repeating motifs; common in nucleic-acid-associated regulators and many viral proteins, and largely absent from structured domains	11.84	16
#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	10.99	2
#7996	Generic extreme N-terminus detector	Generic extreme N-terminus detector: marks residues around position 5 (occasionally 6–7) at the very start of the polypeptide, most often within the N-region of signal/transit peptides of secreted or organelle-targeted precursors, but also in generally disordered N-termini of cytosolic/nuclear proteins; not motif- or residue-specific	10.54	2
#7903	Arginine-rich polybasic patches	Basic polycationic patches enriched in arginine (often with lysine) within low-complexity/disordered regions, frequently N-terminal. These include classical monopartite NLSs, nucleic acid–binding basic tails, signal peptide n-regions and cytosolic juxtamembrane segments (positive-inside rule), and basic clusters in secreted precursors; typically depleted of acidic residues.	8.23	8
#678	Sparse terminal residue peaks	Sparse residue-level activations distributed across short proteins and protein segments, with frequent firing in disordered N-terminal/C-terminal tails as well as in some short transmembrane or compact domains	7.66	16
#14493	Short hydrophobic helical runs	Short hydrophobic helical segments rich in I/V/F (sometimes M), recognized in both membrane-targeting/insertion contexts (signal peptides, signal-anchors, transmembrane helices) and in hydrophobic helical patches within otherwise soluble small proteins. The feature flags contiguous aliphatic/hydrophobic runs across diverse proteins, including viral membrane/accessory proteins, secreted peptide/effector precursors, small ORFs/microproteins, and short basic/uncharacterized human proteins.	7.42	3
#11429	G/S-rich disordered low-complexity	Intrinsically disordered, low‑complexity regions enriched in glycine and serine (with frequent threonine and Q/N tracts)—i.e., SG‑repeat and polar low‑complexity segments—common in eukaryotic regulators and some viral proteins, and largely absent from folded catalytic cores.	7.32	29
#11159	Glycine residue identity detector	Residue-identity detector for glycine (G), largely context-agnostic but with a tendency to fire on glycines in flexible/disordered, often N-terminal or membrane-proximal regions; also active on glycines within transmembrane helices; broadly taxon- and function-independent.	7.19	25
#11504	Initiator methionine at M1	Initiator methionine at the very start of the polypeptide chain (M1), i.e., the translation start residue, independent of protein family, taxonomy, membrane association, or presence of signal/leader/propeptide regions; often annotated as post-translationally removed and typically situated in a flexible, coil-like N-terminus.	6.97	2
#3642	Gly/Ala/Pro-rich disordered segments	Glycine/alanine/proline-rich low-complexity stretches, frequently within annotated disordered regions, that share a recurring small-residue context (Gly-Val/Ala-Xaa-Ala/Pro patterns).	6.91	4
#3454	Disordered C-terminal G/P/S repeats	Short G/P/S-rich low-complexity segments within intrinsically disordered C-terminal tails of bacterial proteins, frequently containing repeated GxG or SGIG/GPG-like sub-motifs with sparsely interspersed R residues	6.75	21
#8488	Ala/Thr-rich N-terminal disorder	Ala/Thr-enriched composition feature with a bias for low-complexity intrinsically disordered regions and N-terminal prepro/signal-peptide segments; the feature reflects small-residue (A/T, secondarily S/P) composition often in flexible regions but also appears at A/T residues in some structured contexts.	6.66	16
#11915	Disordered small-residue tandem repeats	Low-complexity, intrinsically disordered tandem-repeat tracts enriched in small/polar residues (Ser/Thr/Ala/Gly/Pro, often acidic), highlighting simple S/T/A/G/P-rich repeats and flexible non-catalytic tails rather than folded domains; basic and aromatic residues are disfavored.	6.64	25
#9946	Disordered N-termini and coils	Detector for intrinsically disordered, low-structure N‑terminal pre-sequences (signal peptides’ N/C regions, organellar transit peptides, and propeptides) and, more generally, flexible coil/low‑pLDDT segments; strongest bias for the first 10–70 residues but can also mark internal loops in large enzymes and short low‑complexity micropeptides.	6.62	8
#9852	N-terminus activation; hydrophobic helices secondary	Extreme N-terminal regions of proteins, starting at the initiator methionine and extending over a short stretch, with occasional secondary activation at internal hydrophobic/amphipathic helices.	6.49	61
#9234	Charged low-complexity disordered regions	Intrinsically disordered, low-complexity segments enriched for Lys and acidic residues (E/D), plus N/Q, that include both polyampholyte and basic-residue tracts; typically flexible terminal tails and linker regions in diverse eukaryotic and viral proteins, including many small/secreted proteins and membrane-protein loops	6.48	7
#13345	Low-complexity glycine-rich repeats	Small-residue–biased low-complexity repeat regions—typically intrinsically disordered and enriched for Gly and/or Ser/Thr with frequent acidic (Asp/Glu) residues—serving as flexible linkers or mesh-forming domains (e.g., FG repeats in nucleoporins, PTS- or Ser/Thr-rich repeats in mucins/adhesins, glycine-biased linkers of secreted/cell-wall proteins); also includes N/Q-rich LCRs in some taxa (e.g., Apicomplexa) and occasionally captures glycine-periodic repeats such as Gly–X–Y in collagen-like sequences.	5.92	27
#5337	Pro/RGG-rich low-complexity IDRs	Intrinsically disordered, low‑complexity basic segments at termini and long loops, enriched in Pro/Gly and/or Arg/Ser (including RG/RGG or S/T clusters), common across eukaryotic and viral proteins.	5.42	50
#2548	Sticker-spacer tandem-repeat IDRs	Intrinsically disordered, low-complexity tandem-repeat regions (“sticky–spacer” IDRs) enriched in small aliphatic/proline residues with polar/acidic content (P/A/G/V with S/T and D/E), common in secreted/extracellular scaffolds and terminal tails of cytosolic proteins; the feature especially highlights hydrophobic “sticker” residues (often Val/Ala/Phe) embedded within repeat-rich, compositionally biased segments.	5.34	20
#13063	Serine-rich region detector	Serine residues across a wide range of structural contexts, with a bias toward serine-rich segments in intrinsically disordered or low-complexity regions (often N-terminal tails), but also firing on serines within transmembrane helices and other structured contexts; the feature behaves primarily as a serine detector with some preference for S-rich patches.	5.26	3
#11226	N/Q-rich low-complexity IDRs	Intrinsically disordered low-complexity regions specifically enriched for long asparagine and/or glutamine/serine/threonine runs; Pro/Gly content alone is insufficient. Activation is typically in extended linker or terminal tracts outside folded domains and is most common in organisms/proteins that harbor pronounced N/Q-rich repeats.	5.14	40
#5482	N-terminal targeting presequences	Universal eukaryotic N-terminal targeting presequences: the feature detects short, cleavable leader regions at the extreme N-terminus that direct proteins to organelles or the secretory pathway—especially chloroplast/apicoplast transit peptides and thylakoid lumen signals, but also mitochondrial targeting peptides and classical signal peptides. These segments are Ser/Thr- and small/hydrophobic–rich, enriched in Lys/Arg and depleted of acidic residues, typically low-structure/low-confidence and ending at the maturation cleavage site.	4.71	8
#9962	S/T/P-rich disordered regulatory tails	Intrinsically disordered, low‑complexity regions enriched in serine, threonine, proline and polar/charged residues—flexible regulatory linkers/tails and propeptide segments that often host short linear motifs (e.g., phosphorylation- and proline‑rich motifs) and proteolytic processing sites; signal is absent from well‑folded catalytic domains and is common across taxa	4.71	11
#10117	Diffuse low-complexity/disorder signature	A broadly tuned signature of disordered/low-complexity-containing proteins: the feature activates diffusely across long stretches of large multi-domain proteins, with residue-level peaks scattered through both folded and disordered segments. It is common in large, repeat-rich extracellular/surface proteins but also marks regions in diverse intracellular proteins.	4.69	36
#10810	Polar/charged low-complexity regions	Compositionally biased, intrinsically disordered low-complexity segments enriched for polar/charged residues (Q/N/S/T and K/E/D), including homopolymeric tracts (polyQ/polyN), QA/N/S/T repeats, and Lys/acidic clusters; observed across both eukaryotic and bacterial proteins.	4.66	41
#5323	Acidic/polar IDR hotspots	Residue-level detector for acidic/polar hotspots within intrinsically disordered regions (often N‑terminal), with a strong preference for Asp, Asn, His, and Tyr; highlights acidic low‑complexity stretches and flexible loops rather than structured domains	4.57	2
#3278	PRQH-rich disordered tails	Compositionally biased, intrinsically disordered low‑complexity segments enriched in Pro/Arg/Gln/His (frequent PR/PQ tracts, Arg- and His-clusters), with occasional sensitivity to Leu‑rich helical stretches (signal peptides or leucine zippers); typically terminal, widespread across taxa, and common in nucleic‑acid–binding and secreted proteins.	4.54	7
#15970	Serine/threonine-rich disordered linkers	Intrinsically disordered, low‑complexity serine/threonine–rich segments (often containing SP/TP/RS repeats) that function as flexible linkers and phosphorylation‑prone regulatory tracts across diverse proteins, including viral phosphoproteins/nucleocapsid linkers and proline‑rich secreted cell‑wall proteins	4.52	4
#7553	Eukaryotic N-terminal disordered regulatory tails	Eukaryotic N-terminal intrinsically disordered, low-complexity segments of diverse composition (often including S/P/T/G runs, acidic/basic stretches, or proline clusters) that act as regulatory tails/linkers for phosphorylation-dependent signaling and protein–protein interactions.	4.29	44

Feature	Label	Description	Activation	Prevalence
#11775	Disordered C-terminal tail hotspots	Short hotspots in intrinsically disordered terminal tails—most often the cytosolic C-termini of membrane proteins (especially GPCRs and single-pass adhesion proteins), but also analogous termini of soluble proteins.	5.52	2
#13847	Generic polar coil boundary marker	Sparse residue-level feature firing at isolated polar/structured-context positions, often Ser/Thr/Asn/Asp but also basic residues (Arg/Lys), typically in coil or boundary segments of moderately well-structured regions; appears to mark a generic local structural context rather than a function-specific site.	4.12	2
#5613	Junction loops flanking ligand pockets	Short loop/turn segments at secondary-structure junctions that flank or line ligand/cofactor/metal-binding pockets across diverse enzymes, with a characteristic peak on a conserved His/Tyr within an E-T-H/Y-G–type motif in SAM-binding methyltransferases.	3.31	4
#8387	Alpha-helix boundary recognition	Alpha-helix boundary recognition: residues at helix termini (especially C‑caps) and immediately adjacent loop/cap positions, i.e., helix–loop junctions, rather than catalytic or ligand-binding sites	3.19	2
#11248	Short beta-strand loop clusters	Short β-strand/loop segments in non-Ig β-sheet-containing enzymes, including bacterial glycoside hydrolases (amylopullulanases, neopullulanase, isomaltosyltransferase) and eukaryotic molybdo-flavoprotein nitrate reductases.	2.51	2
#11643	Aromatic/cysteine interfacial anchors	Short, aromatic- and cysteine-enriched interfacial helices/patches that mediate contacts at lipid membranes or protein/protein/nucleic-acid interfaces; typified by Trp/Phe clusters and/or palmitoylation‑prone Cys pairs/clusters; these segments act as interfacial anchors or contact elements rather than core transmembrane helices	2.25	2
#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	2.08	2
#8694	Acidic S/T-rich IDRs	Acidic, serine/threonine-rich low-complexity intrinsically disordered regions (often with S/T-P motifs) in eukaryotic nuclear/chromatin-associated proteins, typically residing in long N- or C-terminal regulatory tails enriched for phosphorylation sites.	2.04	2
#9952	Ordered helical assembly scaffold	A broad “ordered helical/assembly scaffold” signature: long, structured segments—often alpha-helical (TM helices, coiled-coils, helical hairpins) and stable cores of ligand/effector-binding domains—that mark architectural elements used for signal transfer and assembly across diverse molecular machines (signaling, secretion, transport, nucleotide/quinone metabolism, and viral replication), rather than specific catalytic micro-motifs.	2.02	4
#6235	Aromatic pocket-gating loop SLiM	A short, aromatic/hydrophobic, helix- or strand-capping loop or linear motif that either lines the entrance/gate of small-molecule/cofactor pockets or forms an exposed docking patch for protein–protein interactions. It recurs across enzymes and helix-grip lipid/ligand carriers (GNAT/NAT acetyltransferases, LuxI AHL synthases, HPPK, Bet v 1/START-like), and also on β-grasp ubiquitin-like modifiers and certain IDR-embedded degrons (e.g., Aux/IAA). Segments are enriched in hydrophobic/aromatic residues with interspersed charges and often feature an aromatic–acidic dyad (W next to D/E) or short W/Y–P–P motifs; when annotated, they map to binding or docking residues.	1.97	2
#630	Cofactor binding loop	A short loop/coil segment lining enzyme active/cofactor-binding pockets, commonly near nucleotide- or cofactor-binding residues across glycosyltransferases, nucleotidyltransferases, and other nucleotide/cofactor-processing enzymes.	1.93	2
#1226	Short basic/aromatic interaction patches	Short basic/aromatic–enriched segments, typically at or just beyond catalytic domains and especially the retroelement integrase C‑terminal module (integrase CTD/GPY‑F region), that often occur as flexible coils or short helices and serve as DNA/chromatin- or partner‑interaction patches; the feature also recognizes analogous Trp‑rich motifs (e.g., PWWP‑like) in diverse proteins.	1.92	2
#6360	N-terminal low-complexity IDRs	Eukaryotic intrinsically disordered, low‑complexity N‑terminal tails enriched in Lys/Arg/Ser/Asp/Glu that precede structured domains of RNA biogenesis/translation and chromatin‑remodeling factors (nucleolar/ssu‑processome, spliceosome/DEAD‑box helicases, H2A.Z chaperones); these flexible segments are typical interaction/assembly regions.	1.89	2
#10131	Conserved aromatic packing hotspots	Aromatic-residue hotspot detector: the feature marks phenylalanine/tyrosine sites that create conserved hydrophobic packing or aromatic-pocket/cage elements within many globular domains and repeat scaffolds, often at analogous positions across duplicated/repeat units.	1.88	2
#2494	Structured-to-disordered boundary segments	A short, terminal or domain-edge coil/loop segment—most often a C‑terminal tail or a loop-to-helix/strand capping region—that marks the transition from a structured core to a flexible/low‑complexity extension. These segments frequently show reduced structural confidence (low pLDDT), are enriched in charged and glycine residues, and occasionally embed specific motifs (e.g., metal-binding cysteines), but typically lack discrete annotated active sites.	1.86	4
#4945	Nucleotidyltransferase phosphate-binding loop	Short glycine‑biased active‑site loop of nucleotidyltransferases that positions the nucleotide triphosphate and helps coordinate catalytic metal ions—i.e., the phosphate‑binding/positioning loop immediately flanking the conserved acidic metal‑binding residues across diverse NTase folds (polymerase/palm, PAP/TUT/CCA‑adding, CD‑NTase/cGAS/OAS, adenylyl/uridylyltransferases, and cytidylyltransferases); often exhibits GxG/GG and nearby aromatic/basic residues.	1.79	2
#5761	Basic helical small protein activation	a broad, whole-protein activation feature for small bacterial and organellar proteins, often helix-rich and Lys/Arg-enriched, with peaks landing on functional helices that engage macromolecular targets — including the HTH DNA-binding modules of transcriptional regulators, internal transmembrane helices of small inner-membrane enzymes, and helical domains of nucleic-acid/protein-binding proteins.	1.78	2
#2308	RNase H-like DDE nuclease core	RNase H–like two‑metal‑ion nuclease catalytic core shared by retroviral integrases and related mobile‑element nucleases (integrases/transposases) and RNase H domains, with strongest signal in the C‑terminal portion of the integrase catalytic domain and adjacent helices surrounding the acidic DDE/DDD metal‑binding site	1.76	2
#1601	Charged helix-capping junction motif	A short, sequence-level motif marking secondary-structure junctions—especially coil/β-strand to α-helix starts, helix capping/termination sites, and β‑hairpin turns—characterized by polar/charged residues with helix-breakers (e.g., Lys/Arg/Glu/His with Pro/Gly/Thr/Ser) and frequent di‑basic Lys pairs. The motif often sits at C-termini or domain boundaries and is frequently adjacent to functional sites (ligand-binding pockets, disulfide/metal linkages), making it a broadly used structural transition/capping signal across taxa and localizations.	1.74	3
#5381	SF2 helicase motif VI loop	Arginine/glycine–rich “motif VI” loop of SF2 helicases in the C‑terminal RecA-like domain—the arginine‑finger–bearing linker (e.g., HRIGRTGR/RTGRFGR/QTRGR) that couples ATP hydrolysis to nucleic‑acid binding/translocation; recognized as a short flexible helix→loop→β-strand junction conserved across RNA and DNA helicase/translocase families (including chromatin remodelers and viral SF2 helicases)	1.72	2
#10820	Short helical activation segments	Short helical or mixed secondary-structure segments within catalytic enzymes (notably M16 family zinc metallopeptidases such as stromal processing peptidase, presequence protease/pitrilysin, and PqqE) and some non-catalytic mitochondrial complex subunits. Activation tends to localize to a C-terminal or internal region of the mature chain, distinct from the active site.	1.71	2
#13047	Membrane-docking amphipathic helices	Short helical patches (often amphipathic and enriched in basic/aromatic residues) embedded within intrinsically disordered linkers or tails, typically positioned immediately C-terminal to signal/translocation motifs, adjacent to transmembrane segments, or at the edge of folded domains/coiled-coils. These helices mediate membrane association or adaptor docking in secretion, trafficking, and virulence contexts.	1.69	2
#10816	Terminal low-complexity interaction tails	Terminal low‑complexity interaction tails (predominantly C‑terminal) that are disordered‑to‑helical segments enriched in polar/charged residues with interspersed hydrophobics, carrying short linear motifs or key residues used for partner docking (protein or nucleic acid), oligomerization, or proximity to regulatory redox sites	1.66	4
#2980	Extracellular and lumenal receptor-binding modules	Extracellular and organelle-lumenal recognition/adhesion modules and their flexible linkers in secreted, surface-exposed, or organelle-targeted proteins—most prominently CBMs and phage tail-spike receptor-binding regions—together with related beta-rich recognition domains (e.g., MAM, MD-2/ML/NPC2, toxin receptor-binding β-domains) and N-terminal segments immediately following signal or transit peptides; the feature avoids catalytic glycosidase cores and transmembranes and favors glycine/serine/threonine- and acidic-rich loops studded with aromatics used for glycan/lipid/protein ligand binding.	1.65	3
#3402	Charged low-complexity interface patches	Short, low-complexity, charged/polar segments and adjacent helical patches (often containing Lys/Arg clusters), used widely across proteins for assembly, targeting, or intra-/inter-subunit contacts and nucleic-acid binding interfaces	1.64	2
#6746	Charged regions and conserved motifs	Charged/polar interaction segments and conserved motifs: the feature highlights mixed-charge segments rich in S/T/E/D/K/R/H that mediate assembly and binding, and also peaks on specific histidine/acidic motifs embedded in structured domains (e.g., HxHxDH in metallo-β-lactamases, GH–WD repeat blades).	1.51	2
#3175	Short disordered C-terminal tail	Short disordered C-terminal (or near-terminal) tracts (~7–10 aa) that drive a single localized activation peak. Compositional bias varies — A/G/S/P-rich, polybasic (K/R-rich), mixed basic/acidic, or cysteine-rich repeat motifs are all observed — so the feature is best characterized by its positional/structural context (short disordered tails or terminal segments) rather than by a single residue composition.	1.47	2
#14850	Active-site cofactor-binding loops	Short, active-site–adjacent segments that bind or coordinate small-molecule cofactors and metal centers—especially FMN/PLP, F420, 2-oxoglutarate, Zn2+, and [4Fe-4S]—and closely related substrate-recognition motifs; typically β-strand/loop or β-turn–β elements (occasionally a short helix), enriched in Gly plus aromatic and charged residues, and located in mid-to-late regions of the protein.	1.46	3
#11022	Conserved loop motif activations	Short conserved sequence motifs in loop/turn regions of diverse enzymes, frequently containing a mix of basic (R/Q), polar (T/N/S), and acidic (D/E) residues, located at internal positions away from the canonical catalytic residues	1.46	2
#13374	Post-cleavage extracellular edge hotspots	Signature of extracytoplasmic/envelope-associated structural regions—preferentially the mature (post-cleavage) portions of virion and surface/secreted proteins and single-pass membrane anchors—with peaks at secondary-structure edges (helix/strand caps, loop→strand transitions and within beta-strands); avoided in signal peptides and well-folded accessory C-terminal domains	1.44	2

Feature	Label	Description	Δ activation	Iso act.	Canon act.	Iso prev.	Canon prev.
#1135	Homopolymeric low-complexity tracts	Compositionally biased, low-complexity sequence segments characterized by homopolymeric residue runs; the feature detects local stretches of repeated single amino acids regardless of chemistry (polar, basic, or hydrophobic), most often within disordered or unstructured contexts but also occasionally within folded domains where such runs occur.	+10.06	11.83	1.77	63	4
#6484	Prion-like low-complexity IDRs	Polar low-complexity intrinsically disordered regions (IDRs)—especially Q/N-rich (prion-like) segments and S/T- and glycine-rich tracts with simple SG/TG/PG repeats—typically located in inter-domain linkers and terminal tails of eukaryotic proteins and often harboring Ser/Thr phosphorylation sites.	+9.76	12.23	2.47	63	3
#6125	Disordered PTM/cleavage SLiMs	Short linear motifs in intrinsically disordered/low-complexity regions, often S/T/P/G- and aromatic-rich, that include proteolytic-processing/PTM hotspots and flexible linkers adjacent to transmembrane segments; the feature favors flexible coils or short amphipathic helices and systematically avoids hydrophobic transmembrane cores	+6.19	8.67	2.48	11	8
#4992	Small-residue disordered N-terminus	Context-dependent free N-terminus signature: short, disordered amino-terminal stretches beginning with the initiator Met followed by residues compatible with MAP cleavage or N-acetylation (e.g., M–G/A/S/T/V, and other contexts including M–D/E/L); strongest emphasis on small residues at positions 2–3; activation is absent when the native N-terminus is structured or starts with a signal peptide/transmembrane segment.	+6.16	17.31	11.15	5	2
#6398	Polar low-complexity disordered stretches	Polar/small-residue-enriched (often Ser/Thr- and Pro-rich) stretches, frequently within intrinsically disordered or low-complexity regions and N-terminal tails/propeptides; can extend into short, flexible helices in small proteins, and is also seen in localized patches within folded domains	+5.35	8.00	2.65	19	11
#9000	Glutamate-biased acidic tract detector	Detector of glutamate identity and glutamate-enriched acidic tracts: strong activation on E residues, especially within acidic, low‑complexity/disordered regions; weaker, sporadic responses on D; largely domain-, function-, and taxonomy-agnostic.	+4.54	9.37	4.82	20	15
#13480	Alanine and small-residue enrichment	A sequence-composition feature that detects small, non-aromatic residues—especially alanine—and their enrichment, lighting up individual Ala residues and stretches enriched in A/G/S/T/P/V (alanine-rich, low-complexity segments) irrespective of protein function or secondary structure.	+4.50	9.25	4.75	22	6
#11023	Low-complexity disordered regions	Intrinsically disordered, low‑complexity segments—often N‑terminal tails or leader/signal regions—enriched in Ser/Pro/Gly/Arg and predicted as coils/low‑confidence structure; the feature marks flexible, poorly structured regions rather than a specific function	+4.39	6.06	1.67	8	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.	+4.39	9.83	5.44	11	10
#9395	Short terminal targeting segment	Terminal or short internal targeting/interaction segment: a short, compositionally biased or hydrophobic patch near a protein terminus, or occasionally an internal low‑complexity loop, that functions as a signal peptide or signal‑anchor (Sec/ER/thylakoid/Tat entry) when hydrophobic, or as a basic/Ser/Lys/Arg/Pro‑rich low‑complexity segment that mediates localization or partner binding in soluble proteins; typically the single prominent terminal segment of short secreted, membrane, or regulatory proteins	+4.22	6.31	2.09	7	4
#8412	Valine-centered residue detector	Detector that fires on valine residues across diverse sequence contexts, including hydrophobic transmembrane helices and signal peptides as well as Val-containing tandem repeats (elastomeric Gly-rich lamprin-like repeats, Pro/Arg-rich disordered repeats) and isolated Val positions in soluble globular proteins.	+4.14	10.31	6.17	11	9
#6356	Ser/Gly/Pro-rich low-complexity IDRs	Often fires on intrinsically disordered, low-complexity regions (IDRs) enriched in Ser/Gly/Pro and basic (Lys/Arg) residues, frequently in secreted/viral proteins, but also activates on short peptides and small folded proteins with no clear sequence motif. Includes Ser-rich PTM-prone segments within unstructured regions.	+4.07	7.25	3.18	32	7
#14891	Disordered termini and cleavage detector	Residue-level detector of intrinsically disordered, flexible termini and proteolytic processing junctions—especially N-termini (including the first residue of the mature chain after propeptide/leader cleavage)—with no strict amino‑acid specificity and a bias toward small/charged residues; common in small, secreted/precursor and viral proteins but also present in disordered regions of diverse proteins.	+4.04	6.91	2.87	21	2
#5021	Polybasic intrinsically disordered regions	Low-complexity, often intrinsically disordered regions in short proteins, precursors, and microproteins across taxa, including viral accessory proteins, neuropeptide/hormone precursors, sperm nuclear proteins, flexible enzyme tails/inserts, and antisense-derived/uncharacterized microproteins. Activation is biased toward, but not restricted to, basic (Lys/Arg) clusters, with frequent peaks also at Pro/Ser/Gly residues in disordered context.	+3.97	5.52	1.54	11	3
#3926	Intrinsic disorder/low-complexity detector	Intrinsic disorder/low-complexity detector: activates on flexible, polar/charged, Q/N/S/T/E/D/K/R- and G/P-enriched segments—often N‑terminal tails—typical of intrinsically disordered regions in small secreted peptides/toxins and viral or eukaryotic regulatory proteins, including Q/N‑rich tracts; signals low-confidence coils or labile helices rather than folded domains.	+3.95	6.25	2.30	9	6
#14056	Q/H-rich low-complexity IDRs	Intrinsically disordered, low‑complexity regions enriched for glutamine and histidine (often with proline/glycine runs)—flexible activation/linker segments that frequently flank structured cores (e.g., DNA‑binding or catalytic domains) in eukaryotic proteins. They are especially common in plant transcription factors, but also occur in secreted peptide precursors and in short terminal tails of enzymes (e.g., Fe(II)/2OG dioxygenases). The feature avoids folded domains and metal‑binding motifs and highlights long polar, compositionally biased coils (including poly‑Q/His patches).	+3.92	7.27	3.35	13	5
#11526	Glycine amidation motif detector	Residue-level detector for small/flexible residues—especially glycine—in short, low-structure linkers and proteolytic processing signals of peptide precursors, with a strong preference for the C‑terminal amidation context in which a glycine (amide donor) immediately precedes mono/di‑basic residues (G‑K/R); outside precursors it gives sparse hits on similar small-residue sites in intrinsically disordered regions and occasionally within structured domains across diverse taxa.	+3.80	6.59	2.79	18	12
#2692	Compositionally biased disordered LCRs	Feature targets compositionally biased, intrinsically disordered low‑complexity regions with long contiguous runs strongly enriched in small/polar (Gly/Ser/Asn/Thr) or acidic (Asp/Glu) residues; occasional activation on highly basic protamine‑like LCRs. Mere disorder, generic tails, or coiled‑coils are insufficient without such compositional bias.	+3.79	7.07	3.29	33	8
#1722	S/T/Pro-rich disordered regions	Intrinsically disordered, low-complexity sequence elements enriched in Ser/Thr/Pro/polar residues, characteristic of flexible linkers, regulatory tails, and polar/low-complexity tracts across diverse taxa.	+3.69	6.80	3.12	22	13
#15526	Polar low-complexity disordered regions	Intrinsically disordered, low‑complexity regions enriched in polar/acidic and amide residues—especially Q/E/S/T/P/G—often including proline‑rich tracts and S/T clusters; these segments are flexible, cysteine‑poor, and typically lie outside structured catalytic cores (e.g., disordered tails, propeptides, and regulatory regions).	+3.62	6.65	3.03	7	7
#13897	Proline-rich IDR detector	Detector of proline residues, with strongest signal in proline-rich, intrinsically disordered, low-complexity segments (often at termini, propeptides, and surface-exposed regions). The feature also activates on more isolated prolines in compact protein contexts, including within transmembrane helices, though typically at lower intensity than in extended Pro-rich disorder.	+3.62	8.07	4.45	16	9
#10931	Polar/proline-rich IDR tails	Compositionally biased, low-complexity segments enriched in polar/proline residues (Q/N/H/P with frequent S/G), typically in intrinsically disordered regions and often in C-terminal tails of transcription factors and other proteins	+3.47	6.05	2.58	6	4
#3054	Basic GP/PTS low-complexity tracts	Intrinsically disordered, low‑complexity segments enriched in glycine/proline and serine/threonine, often containing clusters of basic residues (Lys/Arg) and simple repeats; includes PTS- and GP-rich repeats in secreted/processed peptides and extracellular proteins, as well as basic, Ser/Arg‑rich viral and micropeptide regions. Activation requires extended low‑complexity tracts with these compositions; compact or acidic sequences lacking such tracts are typically not activated.	+3.46	6.25	2.79	22	10
#2038	Disordered low-complexity regulatory regions	Low-complexity, intrinsically disordered regulatory regions enriched for serine/threonine and glutamine/asparagine (often with glycine/proline/histidine runs), typically located in N- or C-terminal tails and flexible linkers of eukaryotic proteins; these segments include transcriptional activation/repression regions and phosphorylation-modulated interaction sites, while structured catalytic or DNA/RNA-binding domains are not targeted.	+3.44	5.39	1.96	60	5
#7583	Short disordered low-complexity segments	Short, intrinsically disordered low-complexity segments—including propeptide regions and other disordered stretches—with a bias toward small (Gly/Pro/Ser/Ala/Asn) and basic (Lys/Arg) residues	+3.23	6.88	3.65	22	12
#9998	Weak N+3 positional cue	Absolute N-terminal positional cue centered near the fourth residue (N+3), independent of amino-acid identity; most often within signal/transit peptides of precursors but also present in non-secreted proteins; the effect is weak and often does not produce a discrete detected site.	+3.10	12.38	9.28	3	3
#787	Basic disordered microprotein regions	The feature activates within small proteins, viral accessory/regulatory proteins, and short ORFs, often on disordered or low-complexity segments. Activation is frequently associated with basic-residue–containing patches (Lys/Arg) but is not restricted to a particular position in the protein.	+3.07	4.97	1.90	19	2
#1803	Unknown generic feature	Unknown generic feature	+11.54	23.66	12.12	245	179
#14534	Unknown generic feature	Unknown generic feature	+8.38	24.86	16.48	246	182
#9005	Unknown generic feature	Unknown generic feature	+8.22	21.06	12.84	209	157

Feature	Label	Description	Activation	Prevalence
#4992	Small-residue disordered N-terminus	Context-dependent free N-terminus signature: short, disordered amino-terminal stretches beginning with the initiator Met followed by residues compatible with MAP cleavage or N-acetylation (e.g., M–G/A/S/T/V, and other contexts including M–D/E/L); strongest emphasis on small residues at positions 2–3; activation is absent when the native N-terminus is structured or starts with a signal peptide/transmembrane segment.	17.31	3
#5725	UBC/E2-like fold recognition	UBC/E2-like fold recognition across ubiquitin and ubiquitin-like conjugation systems, capturing catalytically active E2s and inactive homologs (UEV, RWD) and the cognate ESCRT components that harbor them; the signal corresponds to the conserved UBC-core surface, with a bias toward the N-terminal α-helix, and can extend to physicochemically similar acidic, α-helical blocks that mimic this surface	16.41	64
#6484	Prion-like low-complexity IDRs	Polar low-complexity intrinsically disordered regions (IDRs)—especially Q/N-rich (prion-like) segments and S/T- and glycine-rich tracts with simple SG/TG/PG repeats—typically located in inter-domain linkers and terminal tails of eukaryotic proteins and often harboring Ser/Thr phosphorylation sites.	12.23	63
#15545	Low-complexity disordered regions	Intrinsic disorder/low-complexity segments enriched in small, polar and charged residues (S/T/N/G/A/E/D/R/K), especially N-terminal tails, C-terminal tails, and inter-domain regions that contain short repeating motifs; common in nucleic-acid-associated regulators and many viral proteins, and largely absent from structured domains	11.84	16
#1135	Homopolymeric low-complexity tracts	Compositionally biased, low-complexity sequence segments characterized by homopolymeric residue runs; the feature detects local stretches of repeated single amino acids regardless of chemistry (polar, basic, or hydrophobic), most often within disordered or unstructured contexts but also occasionally within folded domains where such runs occur.	11.83	61
#8412	Valine-centered residue detector	Detector that fires on valine residues across diverse sequence contexts, including hydrophobic transmembrane helices and signal peptides as well as Val-containing tandem repeats (elastomeric Gly-rich lamprin-like repeats, Pro/Arg-rich disordered repeats) and isolated Val positions in soluble globular proteins.	10.31	2
#5241	Early N-terminal positional signal	Generic early N-terminus positional signal peaking at residue ~5–7, found broadly within the disordered N-tail of proteins, including both cleavable leader/targeting segments (signal peptides, propeptides) of precursor proteins and disordered N-terminal regions of mature proteins; residue identity is not specific	10.04	2
#10704	N-terminal PEST-like IDRs	Low-complexity, often acidic/proline-rich intrinsically disordered N-terminal tails of intracellular eukaryotic proteins, frequently overlapping annotated PEST-like segments.	9.84	39
#9000	Glutamate-biased acidic tract detector	Detector of glutamate identity and glutamate-enriched acidic tracts: strong activation on E residues, especially within acidic, low‑complexity/disordered regions; weaker, sporadic responses on D; largely domain-, function-, and taxonomy-agnostic.	9.37	4
#13480	Alanine and small-residue enrichment	A sequence-composition feature that detects small, non-aromatic residues—especially alanine—and their enrichment, lighting up individual Ala residues and stretches enriched in A/G/S/T/P/V (alanine-rich, low-complexity segments) irrespective of protein function or secondary structure.	9.25	16
#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	9.12	4
#627	Generic serine detector	Generic serine detector: the feature marks serine residues, with weaker affinity for threonine (and occasionally proline), and is especially prominent in low-complexity S/T-rich stretches; it is context- and structure-agnostic and does not correspond to a specific functional motif.	8.69	3
#9237	Glycine detector in disordered regions	Residue-identity detector for glycine (G), with a mild bias toward intrinsically disordered/low-complexity segments (often including very N-terminal residues); pan-taxonomic and function-agnostic, but activation is sparse and frequently absent, becoming detectable mainly in glycine-rich low-complexity contexts; occasional weak responses to other small/polar residues.	8.52	25
#7903	Arginine-rich polybasic patches	Basic polycationic patches enriched in arginine (often with lysine) within low-complexity/disordered regions, frequently N-terminal. These include classical monopartite NLSs, nucleic acid–binding basic tails, signal peptide n-regions and cytosolic juxtamembrane segments (positive-inside rule), and basic clusters in secreted precursors; typically depleted of acidic residues.	8.23	8
#13897	Proline-rich IDR detector	Detector of proline residues, with strongest signal in proline-rich, intrinsically disordered, low-complexity segments (often at termini, propeptides, and surface-exposed regions). The feature also activates on more isolated prolines in compact protein contexts, including within transmembrane helices, though typically at lower intensity than in extended Pro-rich disorder.	8.07	5
#6398	Polar low-complexity disordered stretches	Polar/small-residue-enriched (often Ser/Thr- and Pro-rich) stretches, frequently within intrinsically disordered or low-complexity regions and N-terminal tails/propeptides; can extend into short, flexible helices in small proteins, and is also seen in localized patches within folded domains	8.00	5
#4900	Arginine-rich segments and residues	Arginine residue identity/basic-tract feature: primarily marks arginine (R) residues—and dense arginine-rich, low-complexity segments—independent of protein family, fold, or function; shows a strong bias for R over other residues (occasional weak lysine signal), appearing both in disordered/repetitive regions and on individual R within structured domains or near transmembrane boundaries.	8.00	8
#678	Sparse terminal residue peaks	Sparse residue-level activations distributed across short proteins and protein segments, with frequent firing in disordered N-terminal/C-terminal tails as well as in some short transmembrane or compact domains	7.66	16
#14493	Short hydrophobic helical runs	Short hydrophobic helical segments rich in I/V/F (sometimes M), recognized in both membrane-targeting/insertion contexts (signal peptides, signal-anchors, transmembrane helices) and in hydrophobic helical patches within otherwise soluble small proteins. The feature flags contiguous aliphatic/hydrophobic runs across diverse proteins, including viral membrane/accessory proteins, secreted peptide/effector precursors, small ORFs/microproteins, and short basic/uncharacterized human proteins.	7.42	3
#11429	G/S-rich disordered low-complexity	Intrinsically disordered, low‑complexity regions enriched in glycine and serine (with frequent threonine and Q/N tracts)—i.e., SG‑repeat and polar low‑complexity segments—common in eukaryotic regulators and some viral proteins, and largely absent from folded catalytic cores.	7.32	29
#14056	Q/H-rich low-complexity IDRs	Intrinsically disordered, low‑complexity regions enriched for glutamine and histidine (often with proline/glycine runs)—flexible activation/linker segments that frequently flank structured cores (e.g., DNA‑binding or catalytic domains) in eukaryotic proteins. They are especially common in plant transcription factors, but also occur in secreted peptide precursors and in short terminal tails of enzymes (e.g., Fe(II)/2OG dioxygenases). The feature avoids folded domains and metal‑binding motifs and highlights long polar, compositionally biased coils (including poly‑Q/His patches).	7.27	8
#6356	Ser/Gly/Pro-rich low-complexity IDRs	Often fires on intrinsically disordered, low-complexity regions (IDRs) enriched in Ser/Gly/Pro and basic (Lys/Arg) residues, frequently in secreted/viral proteins, but also activates on short peptides and small folded proteins with no clear sequence motif. Includes Ser-rich PTM-prone segments within unstructured regions.	7.25	25
#11159	Glycine residue identity detector	Residue-identity detector for glycine (G), largely context-agnostic but with a tendency to fire on glycines in flexible/disordered, often N-terminal or membrane-proximal regions; also active on glycines within transmembrane helices; broadly taxon- and function-independent.	7.19	25
#2692	Compositionally biased disordered LCRs	Feature targets compositionally biased, intrinsically disordered low‑complexity regions with long contiguous runs strongly enriched in small/polar (Gly/Ser/Asn/Thr) or acidic (Asp/Glu) residues; occasional activation on highly basic protamine‑like LCRs. Mere disorder, generic tails, or coiled‑coils are insufficient without such compositional bias.	7.07	25
#14534	Unknown generic feature	Unknown generic feature	24.86	65
#1803	Unknown generic feature	Unknown generic feature	23.66	65
#9005	Unknown generic feature	Unknown generic feature	21.06	65
#14895	Unknown generic feature	Unknown generic feature	20.17	65
#9214	Unknown generic feature	Unknown generic feature	15.84	65
#9194	Unknown generic feature	Unknown generic feature	13.92	65

Clinical variants

Differential region — N-terminal extension (isoform-unique)

Pos (iso)	AA change	Consequence	Source	Clin. sig.	AF (gnomAD)	Impact	AlphaMissense	ESM-C ΔLLR	Link
0	T→K	missense_variant	gnomAD	—	1.03e-04	—	N/A	—	chr19-58558575-G-T
2	A→A	synonymous_variant	gnomAD	—	7.91e-05	—	N/A	0.00	chr19-58558568-G-A
4	A→V	missense_variant	gnomAD	—	5.55e-05	—	N/A	-1.86	chr19-58558563-G-A
4	A→G	missense_variant	gnomAD	—	5.55e-05	—	N/A	-0.02	chr19-58558563-G-C
7	A→A	synonymous_variant	gnomAD	—	3.49e-05	—	N/A	0.00	chr19-58558553-C-T
14	G→G	synonymous_variant	gnomAD	—	1.85e-05	—	N/A	0.00	chr19-58558532-T-G
14	—	frameshift_variant	gnomAD	—	1.85e-05	LoF	—	—	chr19-58558532-TCCGCTCCTCTCCGCGCCCA-T
15	—	inframe_deletion	gnomAD	—	1.35e-05	—	N/A	—	chr19-58558529-CGCTCCGCTCCTCTCCGCGCCCACCGCGCGGCCCGCCTCG-C
16	A→T	missense_variant	gnomAD	—	1.75e-04	—	N/A	-2.84	chr19-58558528-C-T
18	Q→E	missense_variant	gnomAD	—	9.74e-06	—	N/A	1.02	chr19-58558522-G-C
23	A→E	missense_variant	gnomAD	—	5.45e-06	—	N/A	-1.92	chr19-58558506-G-T
24	A→T	missense_variant	gnomAD	—	1.63e-05	—	N/A	-3.77	chr19-58558504-C-T
25	A→A	synonymous_variant	gnomAD	—	4.53e-06	—	N/A	0.00	chr19-58558499-T-C
26	A→P	missense_variant	gnomAD	—	4.25e-06	—	N/A	-2.91	chr19-58558498-C-G
28	E→K	missense_variant	gnomAD	—	3.55e-06	—	N/A	-2.48	chr19-58558492-C-T
29	A→V	missense_variant	gnomAD	—	3.20e-06	—	N/A	-2.54	chr19-58558488-G-A
30	A→T	missense_variant	gnomAD	—	9.24e-06	—	N/A	-3.92	chr19-58558486-C-T
31	A→V	missense_variant	gnomAD	—	3.71e-05	—	N/A	-2.69	chr19-58558482-G-A
32	A→A	synonymous_variant	gnomAD	—	2.33e-06	—	N/A	0.00	chr19-58558478-C-A
32	A→E	missense_variant	gnomAD	—	2.48e-06	—	N/A	-2.22	chr19-58558479-G-T
34	P→R	missense_variant	gnomAD	—	2.06e-06	—	N/A	1.43	chr19-58558473-G-C
35	R→K	missense_variant	gnomAD	—	7.28e-05	—	N/A	-3.53	chr19-58558470-C-T
36	S→R	missense_variant	gnomAD	—	7.21e-06	—	N/A	1.12	chr19-58558466-G-C
37	G→G	synonymous_variant	gnomAD	—	1.70e-06	—	N/A	0.00	chr19-58558463-T-A
38	G→S	missense_variant	gnomAD	—	2.45e-05	—	N/A	-1.64	chr19-58558462-C-T
40	A→A	synonymous_variant	gnomAD	—	1.46e-06	—	N/A	0.00	chr19-58558454-C-G
40	A→V	missense_variant	gnomAD	—	1.48e-06	—	N/A	-1.44	chr19-58558455-G-A
40	A→E	missense_variant	gnomAD	—	1.48e-06	—	N/A	-1.34	chr19-58558455-G-T
41	G→D	missense_variant	gnomAD	—	1.01e-05	—	N/A	-3.19	chr19-58558452-C-T
43	G→D	missense_variant	gnomAD	—	1.33e-06	—	N/A	-3.21	chr19-58558446-C-T
44	G→A	missense_variant	gnomAD	—	1.34e-06	—	N/A	-0.41	chr19-58558443-C-G
45	G→G	synonymous_variant	gnomAD	—	1.55e-05	—	N/A	0.00	chr19-58558439-C-T
45	G→V	missense_variant	gnomAD	—	1.28e-06	—	N/A	-2.59	chr19-58558440-C-A
45	G→E	missense_variant	gnomAD	—	1.92e-05	—	N/A	-2.25	chr19-58558440-C-T
46	P→L	missense_variant	gnomAD	—	2.50e-06	—	N/A	-1.36	chr19-58558437-G-A
46	P→S	missense_variant	gnomAD	—	1.29e-06	—	N/A	1.17	chr19-58558438-G-A
47	G→D	missense_variant	gnomAD	—	1.24e-06	—	N/A	-3.70	chr19-58558434-C-T
48	G→V	missense_variant	gnomAD	—	1.22e-06	—	N/A	-2.24	chr19-58558431-C-A
49	R→R	synonymous_variant	gnomAD	—	1.19e-06	—	N/A	0.00	chr19-58558427-C-G
49	R→R	synonymous_variant	gnomAD	—	1.19e-06	—	N/A	0.00	chr19-58558427-C-T
49	R→Q	missense_variant	gnomAD	—	9.50e-05	—	N/A	-2.95	chr19-58558428-C-T
49	R→G	missense_variant	gnomAD	—	1.20e-06	—	N/A	1.34	chr19-58558429-G-C
49	R→Q	missense_variant	COSMIC	—	—	—	N/A	-2.95	COSV53043558
50	—	frameshift_variant	gnomAD	—	1.17e-06	LoF	—	—	chr19-58558424-ACCCCGGCCACCCGGCC-A
50	G→D	missense_variant	gnomAD	—	2.33e-06	—	N/A	-2.92	chr19-58558425-C-T
50	—	frameshift_variant	gnomAD	—	4.65e-06	LoF	—	—	chr19-58558425-CCCCGGCCA-C
51	P→P	synonymous_variant	gnomAD	—	1.84e-05	—	N/A	0.00	chr19-58558421-G-A
51	P→S	missense_variant	gnomAD	—	1.12e-06	—	N/A	-0.16	chr19-58558423-G-A
52	G→G	synonymous_variant	gnomAD	—	3.25e-06	—	N/A	0.00	chr19-58558418-C-A
52	G→G	synonymous_variant	COSMIC	—	—	—	N/A	0.00	COSV53042756
53	P→H	missense_variant	gnomAD	—	3.08e-06	—	N/A	-2.28	chr19-58558416-G-T
54	R→H	missense_variant	gnomAD	—	1.88e-06	—	N/A	-3.27	chr19-58558413-C-T
55	G→D	missense_variant	gnomAD	—	9.21e-07	—	N/A	-3.35	chr19-58558410-C-T
55	G→S	missense_variant	gnomAD	—	5.56e-06	—	N/A	-0.93	chr19-58558411-C-T
56	G→G	synonymous_variant	gnomAD	—	2.06e-05	—	N/A	0.00	chr19-58558406-G-A
56	G→D	missense_variant	gnomAD	—	1.78e-06	—	N/A	-3.48	chr19-58558407-C-T
56	G→S	missense_variant	gnomAD	—	6.32e-06	—	N/A	-1.23	chr19-58558408-C-T
57	G→G	synonymous_variant	gnomAD	—	8.77e-07	—	N/A	0.00	chr19-58558403-G-T
57	—	inframe_deletion	gnomAD	—	1.75e-06	—	N/A	—	chr19-58558403-GCCGCCGCCGCGGGGCCCGGGACCCCGGCCACCCGGCCCC-G
57	G→V	missense_variant	gnomAD	—	1.75e-06	—	N/A	-3.30	chr19-58558404-C-A
57	G→C	missense_variant	gnomAD	—	1.77e-06	—	N/A	-3.39	chr19-58558405-C-A
57	G→R	missense_variant	gnomAD	—	2.65e-06	—	N/A	-1.29	chr19-58558405-C-G
57	G→S	missense_variant	gnomAD	—	2.14e-04	—	N/A	-1.64	chr19-58558405-C-T
58	S→I	missense_variant	gnomAD	—	8.60e-07	—	N/A	-4.58	chr19-58558401-C-A
58	S→G	missense_variant	gnomAD	—	3.43e-05	—	N/A	3.43	chr19-58558402-T-C
58	—	inframe_insertion	gnomAD	—	1.32e-05	—	N/A	—	chr19-58558402-T-TGCC
58	—	inframe_insertion	gnomAD	—	1.76e-06	—	N/A	—	chr19-58558402-T-TGCCGCC
58	—	inframe_insertion	gnomAD	—	1.76e-06	—	N/A	—	chr19-58558402-T-TGCCGCCGCC
58	—	inframe_deletion	gnomAD	—	1.23e-05	—	N/A	—	chr19-58558402-TGCCGCC-T
58	—	inframe_deletion	gnomAD	—	1.76e-06	—	N/A	—	chr19-58558402-TGCCGCCGCC-T
58	S→G	missense_variant	COSMIC	—	—	—	N/A	3.43	COSV53040858
59	G→G	synonymous_variant	gnomAD	—	8.52e-07	—	N/A	0.00	chr19-58558397-G-T
59	—	inframe_deletion	gnomAD	—	5.16e-05	—	N/A	—	chr19-58558399-CGCT-C
59	G→S	missense_variant	COSMIC	—	—	—	N/A	-2.09	COSV53040494
60	G→C	missense_variant	gnomAD	—	1.70e-06	—	N/A	-3.83	chr19-58558396-C-A
60	—	inframe_deletion	gnomAD	—	6.80e-06	—	N/A	—	chr19-58558396-CGCCGCT-C
61	G→G	synonymous_variant	gnomAD	—	8.18e-07	—	N/A	0.00	chr19-58558391-G-T
61	G→S	missense_variant	gnomAD	—	8.20e-07	—	N/A	-1.97	chr19-58558393-C-T
61	—	inframe_deletion	gnomAD	—	1.56e-05	—	N/A	—	chr19-58558393-CGCCGCCGCT-C
61	G→S	missense_variant	COSMIC	—	—	—	N/A	-1.97	COSV107228768
62	G→G	synonymous_variant	gnomAD	—	8.16e-07	—	N/A	0.00	chr19-58558388-G-T
62	—	frameshift_variant	gnomAD	—	8.16e-07	LoF	—	—	chr19-58558388-GC-G
62	G→C	missense_variant	gnomAD	—	8.14e-07	—	N/A	-4.17	chr19-58558390-C-A
62	—	inframe_insertion	gnomAD	—	2.44e-06	—	N/A	—	chr19-58558390-C-CGCCGCCGCCGCT
62	—	inframe_deletion	gnomAD	—	8.96e-06	—	N/A	—	chr19-58558390-CGCCGCCGCCGCT-C
63	G→V	missense_variant	gnomAD	—	8.44e-07	—	N/A	-3.26	chr19-58558386-C-A
64	—	inframe_insertion	gnomAD	—	1.56e-06	—	N/A	—	chr19-58558382-C-CCTGCCG
64	R→K	missense_variant	gnomAD	—	7.83e-07	—	N/A	0.12	chr19-58558383-C-T
64	R→W	missense_variant	gnomAD	—	7.99e-07	—	N/A	-5.89	chr19-58558384-T-A
64	R→G	missense_variant	gnomAD	—	7.99e-07	—	N/A	0.89	chr19-58558384-T-C
64	—	inframe_insertion	gnomAD	—	8.78e-05	—	N/A	—	chr19-58558384-T-TGCC
64	—	inframe_insertion	gnomAD	—	7.99e-06	—	N/A	—	chr19-58558384-T-TGCCGCC
64	—	inframe_insertion	gnomAD	—	5.59e-06	—	N/A	—	chr19-58558384-T-TGCCGCCGCC
64	—	inframe_deletion	gnomAD	—	5.56e-04	—	N/A	—	chr19-58558384-TGCC-T
64	—	inframe_deletion	gnomAD	—	1.92e-05	—	N/A	—	chr19-58558384-TGCCGCC-T
64	—	inframe_deletion	gnomAD	—	1.12e-05	—	N/A	—	chr19-58558384-TGCCGCCGCC-T

96 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
65	—	inframe_deletion	gnomAD	—	7.86e-07	—	—	—	chr19-58558381-TCCTGCCGCCGCCGCCGCC-T
66	I→M	missense_variant	gnomAD	—	7.54e-07	damaging	likely_pathogenic (0.66)	-9.12	chr19-58558376-G-C
68	L→L	synonymous_variant	gnomAD	—	7.42e-07	—	—	0.00	chr19-58558370-C-A
68	L→L	synonymous_variant	gnomAD	—	1.48e-06	—	—	0.00	chr19-58558370-C-T
69	F→L	missense_variant	gnomAD	—	7.16e-07	damaging	likely_pathogenic (0.99)	-7.19	chr19-58558367-G-C
70	S→S	synonymous_variant	gnomAD	—	6.38e-06	—	—	0.00	chr19-58558364-C-T
71	L→L	synonymous_variant	gnomAD	—	1.42e-06	—	—	0.00	chr19-58558361-C-T
71	L→L	synonymous_variant	gnomAD	—	6.38e-06	—	—	0.00	chr19-58558363-G-A
71	L→P	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.98)	-12.25	COSV104570910
72	K→K	synonymous_variant	gnomAD	—	6.28e-06	—	—	0.00	chr19-58558358-C-T
73	Q→H	missense_variant	gnomAD	—	1.39e-06	damaging	ambiguous (0.51)	-7.81	chr19-58558355-C-G
73	Q→Q	synonymous_variant	gnomAD	—	5.56e-06	—	—	0.00	chr19-58558355-C-T
73	Q→K	missense_variant	gnomAD	—	6.98e-07	damaging	likely_benign (0.28)	-9.68	chr19-58558357-G-T
74	Q→Q	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV107228773
75	K→K	synonymous_variant	gnomAD	—	6.94e-07	—	—	0.00	chr19-58558349-C-T
75	K→Q	missense_variant	gnomAD	—	8.65e-05	damaging	likely_benign (0.19)	-9.87	chr19-58558351-T-G
75	—	inframe_deletion	gnomAD	—	1.40e-06	—	—	—	chr19-58558351-TCTG-T
75	K→Q	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_benign (0.19)	-9.87	ClinVar:3465079
75	—	inframe_deletion	COSMIC	—	—	—	—	—	COSV99285296
75	K→*	stop_gained	COSMIC	—	—	LoF	—	—	COSV108753444
75	K→E	missense_variant	COSMIC	—	—	damaging	ambiguous (0.56)	-10.75	COSV99285037
76	K→N	missense_variant	gnomAD	—	1.39e-06	damaging	likely_pathogenic (0.72)	-9.06	chr19-58558346-C-A
76	K→K	synonymous_variant	gnomAD	—	6.94e-07	—	—	0.00	chr19-58558346-C-T
76	K→E	missense_variant	gnomAD	—	5.65e-05	damaging	ambiguous (0.45)	-8.94	chr19-58558348-T-C
76	K→Q	missense_variant	gnomAD	—	6.97e-07	damaging	likely_benign (0.22)	-8.25	chr19-58558348-T-G
76	K→E	missense_variant	ClinVar	Uncertain significance	—	damaging	ambiguous (0.45)	-8.94	ClinVar:3185534
76	K→E	missense_variant	COSMIC	—	—	damaging	ambiguous (0.45)	-8.94	COSV99285294
77	E→E	synonymous_variant	gnomAD	—	6.93e-07	—	—	0.00	chr19-58558343-C-T
77	—	inframe_deletion	gnomAD	—	7.63e-06	—	—	—	chr19-58558345-CCTT-C
77	—	inframe_deletion	COSMIC	—	—	—	—	—	COSV53040527
77	E→*	stop_gained	COSMIC	—	—	LoF	—	—	COSV53041176
78	E→D	missense_variant	gnomAD	—	6.92e-07	—	likely_benign (0.09)	-6.03	chr19-58558340-C-G
78	E→Q	missense_variant	gnomAD	—	6.93e-07	damaging	likely_benign (0.24)	-8.31	chr19-58558342-C-G
78	E→K	missense_variant	gnomAD	—	6.93e-07	damaging	ambiguous (0.42)	-8.62	chr19-58558342-C-T
79	E→E	synonymous_variant	gnomAD	—	6.92e-07	—	—	0.00	chr19-58558337-C-T
79	E→A	missense_variant	gnomAD	—	1.60e-05	damaging	likely_benign (0.17)	-7.81	chr19-58558338-T-G
79	E→*	stop_gained	gnomAD	—	1.59e-05	LoF	—	—	chr19-58558339-C-A
80	S→S	synonymous_variant	gnomAD	—	2.07e-06	—	—	0.00	chr19-58558334-C-G
80	S→L	missense_variant	gnomAD	—	2.07e-06	—	likely_benign (0.13)	-7.11	chr19-58558335-G-A
80	—	inframe_insertion	gnomAD	—	1.39e-06	—	—	—	chr19-58558336-A-ACTC
80	S→P	missense_variant	gnomAD	—	2.78e-06	damaging	likely_benign (0.23)	-8.26	chr19-58558336-A-G
80	S→A	missense_variant	COSMIC	—	—	—	likely_benign (0.06)	-5.17	COSV53042996
81	A→V	missense_variant	gnomAD	—	4.15e-06	—	likely_benign (0.10)	-5.07	chr19-58558332-G-A
81	A→V	missense_variant	ClinVar	—	—	—	likely_benign (0.10)	-5.07	ClinVar:4446113
81	A→V	missense_variant	COSMIC	—	—	—	likely_benign (0.10)	-5.07	COSV53041239
82	G→D	missense_variant	COSMIC	—	—	—	likely_benign (0.29)	-7.07	COSV53040529
83	G→R	missense_variant	gnomAD	—	6.91e-07	—	ambiguous (0.46)	-3.38	chr19-58558327-C-G
83	G→S	missense_variant	gnomAD	—	6.91e-07	—	likely_benign (0.08)	-4.44	chr19-58558327-C-T
84	T→T	synonymous_variant	gnomAD	—	6.91e-07	—	—	0.00	chr19-58558322-G-C
84	T→S	missense_variant	gnomAD	—	6.91e-07	—	likely_benign (0.07)	-4.42	chr19-58558324-T-A
85	K→K	synonymous_variant	gnomAD	—	1.38e-06	—	—	0.00	chr19-58558319-C-T
86	G→G	synonymous_variant	gnomAD	—	2.76e-06	—	—	0.00	chr19-58558316-G-A
86	G→G	synonymous_variant	gnomAD	—	6.90e-07	—	—	0.00	chr19-58558316-G-C
86	G→S	missense_variant	gnomAD	—	4.14e-06	—	likely_benign (0.08)	-1.31	chr19-58558318-C-T
87	S→G	missense_variant	COSMIC	—	—	—	likely_benign (0.06)	-3.12	COSV99285000
88	S→N	missense_variant	gnomAD	—	6.89e-07	—	likely_benign (0.13)	-4.49	chr19-58558311-C-T
88	S→G	missense_variant	gnomAD	—	6.21e-06	—	likely_benign (0.06)	-3.87	chr19-58558312-T-C
88	S→R	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.69)	-9.52	COSV53042721
89	—	inframe_deletion	gnomAD	—	4.36e-05	—	—	—	chr19-58558308-TTGC-T
90	K→K	synonymous_variant	gnomAD	—	1.38e-06	—	—	0.00	chr19-58558304-C-T
91	A→A	synonymous_variant	gnomAD	—	6.89e-07	—	—	0.00	chr19-58558301-C-T
91	A→V	missense_variant	gnomAD	—	2.07e-06	—	ambiguous (0.39)	-6.93	chr19-58558302-G-A
91	—	inframe_deletion	gnomAD	—	6.89e-07	—	—	—	chr19-58558303-CCTT-C
93	A→A	synonymous_variant	gnomAD	—	2.07e-06	—	—	0.00	chr19-58558295-C-T
93	A→A	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99285258
93	A→V	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.95)	-9.19	COSV99285056
94	A→A	synonymous_variant	gnomAD	—	9.65e-06	—	—	0.00	chr19-58558292-C-T
96	L→L	synonymous_variant	gnomAD	—	6.89e-07	—	—	0.00	chr19-58558286-C-A
96	L→P	missense_variant	gnomAD	—	6.90e-07	damaging	likely_pathogenic (1.00)	-13.31	chr19-58558287-A-G
96	L→L	synonymous_variant	gnomAD	—	6.89e-07	—	—	0.00	chr19-58558288-G-A
97	R→R	synonymous_variant	gnomAD	—	6.89e-07	—	—	0.00	chr19-58558283-C-G
97	R→W	missense_variant	gnomAD	—	6.90e-07	damaging	likely_pathogenic (1.00)	-11.81	chr19-58558285-G-A
97	R→R	synonymous_variant	gnomAD	—	5.52e-06	—	—	0.00	chr19-58558285-G-T
97	R→W	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.81	COSV108753443
98	I→F	missense_variant	gnomAD	—	6.90e-07	damaging	likely_pathogenic (0.92)	-11.00	chr19-58558282-T-A
99	Q→Q	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53043369
99	Q→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.60)	-10.37	COSV53042340
100	K→E	missense_variant	gnomAD	—	6.92e-07	damaging	likely_pathogenic (0.99)	-10.44	chr19-58558276-T-C
100	K→N	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-10.00	COSV53041909
100	K→R	missense_variant	COSMIC	—	—	damaging	likely_benign (0.29)	-8.50	COSV99285214
101	D→D	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58557156-G-A
102	I→V	missense_variant	gnomAD	—	1.27e-04	—	likely_benign (0.16)	-7.12	chr19-58557155-T-C
102	I→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-12.75	COSV53041425
104	E→*	stop_gained	COSMIC	—	—	LoF	—	—	COSV99285104
105	L→L	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-58557144-C-T
105	L→L	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58557146-G-A
105	L→L	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53043101
106	N→N	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58557141-G-A
107	L→L	synonymous_variant	gnomAD	—	6.16e-06	—	—	0.00	chr19-58557138-C-A
107	L→L	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58557138-C-T
110	T→T	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58557129-C-A
110	T→T	synonymous_variant	gnomAD	—	3.42e-06	—	—	0.00	chr19-58557129-C-T
110	T→M	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.87)	-8.67	COSV99285409
112	D→G	missense_variant	gnomAD	—	6.84e-07	damaging	likely_benign (0.25)	-7.86	chr19-58557124-T-C
112	D→H	missense_variant	gnomAD	—	6.84e-07	damaging	likely_benign (0.24)	-8.55	chr19-58557125-C-G
112	D→N	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.10)	-6.49	chr19-58557125-C-T
113	I→T	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (0.74)	-6.62	chr19-58557121-A-G
113	I→F	missense_variant	gnomAD	—	6.84e-07	damaging	ambiguous (0.50)	-10.50	chr19-58557122-T-A
113	—	frameshift_variant	COSMIC	—	—	LoF	—	—	COSV53043033
113	I→V	missense_variant	COSMIC	—	—	—	likely_benign (0.11)	-6.81	COSV99284991
114	S→S	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58557117-G-A
114	S→I	missense_variant	gnomAD	—	2.84e-03	—	likely_benign (0.11)	-6.87	chr19-58557118-C-A
114	S→T	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.06)	-3.13	chr19-58557118-C-G
114	S→N	missense_variant	gnomAD	—	2.74e-06	—	likely_benign (0.11)	-3.19	chr19-58557118-C-T
114	S→I	missense_variant	ClinVar	—	—	—	likely_benign (0.11)	-6.87	ClinVar:4446110
114	S→R	missense_variant	COSMIC	—	—	damaging	ambiguous (0.36)	-7.77	COSV53042718
115	F→L	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (1.00)	-9.19	chr19-58557116-A-G
115	F→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-9.19	COSV105860227
116	S→S	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58557111-T-C
117	D→E	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.21)	-5.30	chr19-58557108-A-C
117	D→D	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-58557108-A-G
117	D→H	missense_variant	gnomAD	—	6.84e-07	damaging	ambiguous (0.45)	-9.68	chr19-58557110-C-G
117	D→N	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.13)	-5.90	chr19-58557110-C-T
118	P→A	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.08)	-5.76	chr19-58557107-G-C
118	P→T	missense_variant	gnomAD	—	5.54e-05	—	likely_benign (0.10)	-5.89	chr19-58557107-G-T
118	P→T	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.10)	-5.89	ClinVar:3185533
119	D→D	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-58557102-G-A
119	D→E	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.17)	-5.87	chr19-58557102-G-T
119	D→Y	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.69)	-11.56	COSV107228791
120	D→D	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58557099-G-A
120	D→N	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.23)	-7.31	chr19-58557101-C-T
120	D→N	missense_variant	COSMIC	—	—	—	likely_benign (0.23)	-7.31	COSV105017442
121	L→L	synonymous_variant	gnomAD	—	1.37e-05	—	—	0.00	chr19-58557096-G-A
121	L→L	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58557096-G-C
121	L→F	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.59)	-7.75	chr19-58557098-G-A
121	L→I	missense_variant	gnomAD	—	6.84e-07	damaging	likely_benign (0.20)	-8.56	chr19-58557098-G-T
122	L→L	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58557093-G-T
122	L→I	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.69)	-9.31	COSV99285506
123	N→T	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.15)	-6.19	chr19-58557091-T-G
123	N→S	missense_variant	COSMIC	—	—	—	likely_benign (0.09)	-5.69	COSV99285507
124	F→L	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-9.19	chr19-58557087-G-C
125	K→N	missense_variant	gnomAD	—	9.58e-06	—	ambiguous (0.54)	-5.53	chr19-58557084-C-A
125	K→K	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58557084-C-T
126	L→L	synonymous_variant	gnomAD	—	6.16e-06	—	—	0.00	chr19-58557083-G-A
126	L→L	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53043643
127	V→V	synonymous_variant	gnomAD	—	1.57e-05	—	—	0.00	chr19-58557078-G-A
128	I→F	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.93)	-9.55	chr19-58557077-T-A
129	C→C	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58557072-A-G
129	C→S	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.12)	-2.29	chr19-58557073-C-G
129	C→S	missense_variant	COSMIC	—	—	—	likely_benign (0.12)	-2.29	COSV53040817
130	P→P	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58557069-A-T
133	G→G	synonymous_variant	gnomAD	—	6.16e-06	—	—	0.00	chr19-58556928-G-A
133	G→D	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-10.00	COSV106089309
134	F→L	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.95)	-5.01	chr19-58556925-G-C
135	Y→Y	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58556922-G-A
136	K→E	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.64)	-10.28	COSV53397009
137	S→N	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.08)	-4.50	chr19-58556917-C-T
137	S→N	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.08)	-4.50	ClinVar:4601254
138	G→G	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58556913-C-G
139	K→K	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556910-C-T
139	K→K	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99448181
141	V→V	synonymous_variant	gnomAD	—	8.21e-06	—	—	0.00	chr19-58556904-C-T
141	V→A	missense_variant	gnomAD	—	4.79e-06	—	likely_benign (0.23)	-4.70	chr19-58556905-A-G
141	V→L	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.17)	-4.49	chr19-58556906-C-G
141	—	frameshift_variant	COSMIC	—	—	LoF	—	—	COSV53396861
143	S→T	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.08)	-3.66	ClinVar:2277650
143	S→G	missense_variant	COSMIC	—	—	—	likely_benign (0.20)	-6.64	COSV53396524
145	K→K	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556892-C-T
145	K→Q	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.19)	-7.17	chr19-58556894-T-G
145	K→Q	missense_variant	COSMIC	—	—	—	likely_benign (0.19)	-7.17	COSV104386669
148	Q→R	missense_variant	gnomAD	—	6.92e-07	damaging	ambiguous (0.41)	-8.73	chr19-58556783-T-C
148	Q→E	missense_variant	gnomAD	—	6.91e-07	—	likely_benign (0.17)	-7.14	chr19-58556784-G-C
149	G→D	missense_variant	gnomAD	—	6.92e-07	damaging	likely_pathogenic (0.92)	-9.43	chr19-58556780-C-T
150	Y→Y	synonymous_variant	gnomAD	—	3.48e-06	—	—	0.00	chr19-58556776-G-A
150	Y→C	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.94	COSV53397310
151	P→P	synonymous_variant	gnomAD	—	6.99e-07	—	—	0.00	chr19-58556773-C-G
151	P→P	synonymous_variant	gnomAD	—	5.31e-05	—	—	0.00	chr19-58556773-C-T
151	P→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.81	COSV105017440
154	P→P	synonymous_variant	gnomAD	—	3.51e-06	—	—	0.00	chr19-58556764-G-T
154	P→P	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53397969
154	P→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-11.56	COSV104582061
155	P→H	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-13.19	COSV53396325
156	K→K	synonymous_variant	gnomAD	—	7.03e-07	—	—	0.00	chr19-58556758-C-T
156	K→N	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-10.37	COSV104582067
157	V→V	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99448318
160	E→E	synonymous_variant	gnomAD	—	2.13e-06	—	—	0.00	chr19-58556746-C-T
161	T→S	missense_variant	gnomAD	—	1.42e-06	—	ambiguous (0.45)	-6.94	chr19-58556745-T-A
162	M→I	missense_variant	gnomAD	—	7.15e-07	—	ambiguous (0.45)	-6.16	chr19-58556740-C-T
162	M→V	missense_variant	gnomAD	—	2.86e-06	—	likely_benign (0.10)	-6.38	chr19-58556742-T-C
163	V→I	missense_variant	gnomAD	—	7.15e-07	—	likely_benign (0.20)	-6.56	chr19-58556739-C-T
163	V→V	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53397937
163	V→V	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99447899
164	—	frameshift_variant	COSMIC	—	—	LoF	—	—	COSV108778103
165	H→H	synonymous_variant	gnomAD	—	3.58e-06	—	—	0.00	chr19-58556731-G-A
167	N→N	synonymous_variant	gnomAD	—	7.19e-07	—	—	0.00	chr19-58556725-G-A
167	N→S	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.95)	-9.87	COSV53397279
171	E→E	synonymous_variant	gnomAD	—	4.35e-06	—	—	0.00	chr19-58556713-C-T
171	E→Q	missense_variant	gnomAD	—	7.24e-07	damaging	ambiguous (0.36)	-7.90	chr19-58556715-C-G
171	E→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.79)	-9.99	COSV99448054
172	G→G	synonymous_variant	gnomAD	—	1.45e-06	—	—	0.00	chr19-58556710-G-A
173	N→N	synonymous_variant	gnomAD	—	2.90e-06	—	—	0.00	chr19-58556707-G-A
173	N→D	missense_variant	gnomAD	—	7.25e-07	damaging	likely_pathogenic (0.94)	-11.25	chr19-58556709-T-C
174	V→V	synonymous_variant	gnomAD	—	2.90e-06	—	—	0.00	chr19-58556704-G-T
174	V→V	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53396988
174	V→I	missense_variant	COSMIC	—	—	—	likely_benign (0.24)	-5.68	COSV53398436
176	L→L	synonymous_variant	gnomAD	—	2.91e-05	—	—	0.00	chr19-58556698-G-A
176	L→L	synonymous_variant	gnomAD	—	7.26e-07	—	—	0.00	chr19-58556698-G-C
176	L→P	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.62	COSV53396431
177	N→N	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53396949
177	N→I	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-14.37	COSV99448459
178	I→I	synonymous_variant	gnomAD	—	6.90e-05	—	—	0.00	chr19-58556692-G-A
178	I→I	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99448409
179	L→L	synonymous_variant	gnomAD	—	2.18e-06	—	—	0.00	chr19-58556689-G-A
179	L→V	missense_variant	gnomAD	—	7.27e-07	damaging	likely_pathogenic (0.99)	-11.19	chr19-58556691-G-C
180	R→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.98)	-10.19	COSV105017435
180	R→G	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-10.94	COSV53397088
181	E→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-10.12	COSV53398088
182	D→N	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-10.19	COSV99448338
183	W→*	stop_gained	COSMIC	—	—	LoF	—	—	COSV99448402
184	K→T	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.96)	-12.50	COSV53396567
185	P→P	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556364-T-A
185	P→P	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556364-T-G
185	—	frameshift_variant	COSMIC	—	—	LoF	—	—	COSV108778102
185	P→T	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-12.31	COSV99448416
186	V→V	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556361-G-T
187	L→R	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-14.44	COSV108778100
188	T→T	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556355-C-G
188	T→T	synonymous_variant	gnomAD	—	4.10e-06	—	—	0.00	chr19-58556355-C-T
188	T→T	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99447934
189	I→V	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.11)	-7.31	chr19-58556354-T-C
190	N→N	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556349-G-A
191	S→Y	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-12.00	COSV53396807
192	I→V	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.13)	-5.06	ClinVar:4601253
192	I→V	missense_variant	COSMIC	—	—	—	likely_benign (0.13)	-5.06	COSV105872211
193	I→M	missense_variant	ClinVar	—	—	damaging	likely_pathogenic (0.69)	-8.56	ClinVar:4446107
195	G→G	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-58556334-G-A
196	L→L	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556331-C-T
196	—	frameshift_variant	COSMIC	—	—	LoF	—	—	COSV108055283
197	Q→H	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.97)	-11.31	COSV99448490
197	Q→*	stop_gained	COSMIC	—	—	LoF	—	—	COSV99447996
198	Y→*	stop_gained	COSMIC	—	—	LoF	—	—	COSV108055273
199	L→L	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556322-G-A
199	L→L	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53396965
202	E→E	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556227-C-T
202	E→K	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-10.94	chr19-58556229-C-T
202	E→*	stop_gained	ClinVar	—	—	LoF	—	—	ClinVar:4446103
202	E→Q	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.90)	-11.12	COSV53396619
203	P→P	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58556224-G-A
204	N→N	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53397780
205	P→P	synonymous_variant	gnomAD	—	8.26e-03	—	—	0.00	chr19-58556218-G-A
205	P→P	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-58556218-G-C
206	E→*	stop_gained	gnomAD	—	6.84e-07	LoF	—	—	chr19-58556217-C-A
206	E→K	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (0.91)	-9.81	chr19-58556217-C-T
208	P→P	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556209-T-G
209	L→L	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556206-C-T
210	N→N	synonymous_variant	gnomAD	—	4.10e-06	—	—	0.00	chr19-58556203-G-A
211	K→K	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556200-C-T
211	K→T	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.95)	-9.50	chr19-58556201-T-G
212	E→E	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556197-C-T
212	E→D	missense_variant	COSMIC	—	—	—	likely_benign (0.13)	-4.80	COSV53398288
213	A→A	synonymous_variant	gnomAD	—	2.46e-05	—	—	0.00	chr19-58556194-G-A
214	A→T	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-9.75	chr19-58556193-C-T
215	E→D	missense_variant	gnomAD	—	7.52e-06	—	likely_benign (0.11)	-5.28	chr19-58556188-C-A
215	E→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.64)	-10.56	COSV53397401
216	V→V	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-58556185-G-A
216	V→V	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58556185-G-T
216	V→F	missense_variant	gnomAD	—	1.71e-05	damaging	likely_pathogenic (0.75)	-10.36	chr19-58556187-C-A
217	L→L	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58556182-C-G
218	Q→R	missense_variant	gnomAD	—	2.74e-06	—	likely_benign (0.24)	-5.49	chr19-58556180-T-C
218	Q→*	stop_gained	COSMIC	—	—	LoF	—	—	COSV53398029
219	N→S	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.07)	-1.12	chr19-58556177-T-C
220	N→S	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.17)	-5.62	chr19-58556174-T-C
220	N→D	missense_variant	gnomAD	—	6.84e-07	damaging	likely_benign (0.26)	-7.56	chr19-58556175-T-C
221	R→Q	missense_variant	gnomAD	—	1.37e-06	—	ambiguous (0.49)	-7.12	chr19-58556171-C-T
221	R→Q	missense_variant	COSMIC	—	—	—	ambiguous (0.49)	-7.12	COSV53398017
221	R→W	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.83)	-8.50	COSV53397113
222	R→R	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556167-C-T
222	R→Q	missense_variant	gnomAD	—	2.74e-06	damaging	likely_benign (0.30)	-8.62	chr19-58556168-C-T
222	R→W	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (0.68)	-8.37	chr19-58556169-G-A
222	R→W	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.68)	-8.37	COSV53398430
223	L→M	missense_variant	COSMIC	—	—	—	likely_benign (0.11)	-4.24	COSV99448365
224	F→Y	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.76)	-8.37	chr19-58556162-A-T
224	F→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-9.00	COSV53397334
225	E→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.87)	-10.99	COSV99448026
225	E→Q	missense_variant	COSMIC	—	—	—	ambiguous (0.39)	-7.06	COSV99447931
226	Q→Q	synonymous_variant	gnomAD	—	3.42e-06	—	—	0.00	chr19-58556155-C-T
226	Q→L	missense_variant	gnomAD	—	3.42e-06	—	likely_benign (0.21)	-7.43	chr19-58556156-T-A
226	Q→H	missense_variant	COSMIC	—	—	—	ambiguous (0.40)	-6.68	COSV99447946
226	Q→L	missense_variant	COSMIC	—	—	—	likely_benign (0.21)	-7.43	COSV53397103
227	N→N	synonymous_variant	gnomAD	—	3.41e-04	—	—	0.00	chr19-58556152-G-A
228	V→V	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556149-C-T
229	Q→H	missense_variant	gnomAD	—	4.52e-05	—	likely_benign (0.15)	-4.12	chr19-58556146-C-A
229	Q→Q	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-58556146-C-T
229	Q→H	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.15)	-4.12	ClinVar:2512439
230	R→R	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58556143-G-A
230	R→H	missense_variant	gnomAD	—	1.37e-06	damaging	ambiguous (0.40)	-9.21	chr19-58556144-C-T
230	R→H	missense_variant	ClinVar	Uncertain significance	—	damaging	ambiguous (0.40)	-9.21	ClinVar:3976736
230	R→H	missense_variant	COSMIC	—	—	damaging	ambiguous (0.40)	-9.21	COSV53397913
230	R→G	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.73)	-11.58	COSV53397160
231	S→F	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-10.50	chr19-58556141-G-A
232	M→T	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.95)	-7.23	chr19-58556138-A-G
232	M→V	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.30)	-5.77	chr19-58556139-T-C
232	M→L	missense_variant	gnomAD	—	6.84e-07	—	likely_benign (0.16)	-2.62	chr19-58556139-T-G
233	R→P	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-13.93	chr19-58556135-C-G
233	R→Q	missense_variant	gnomAD	—	6.84e-07	damaging	likely_benign (0.22)	-8.25	chr19-58556135-C-T
233	R→W	missense_variant	gnomAD	—	2.05e-06	damaging	likely_pathogenic (0.68)	-11.12	chr19-58556136-G-A
233	R→G	missense_variant	gnomAD	—	6.84e-07	damaging	ambiguous (0.52)	-9.56	chr19-58556136-G-C
233	R→R	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-58556136-G-T
233	R→W	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.68)	-11.12	COSV53397232
234	G→G	synonymous_variant	gnomAD	—	9.17e-05	—	—	0.00	chr19-58556131-A-G
234	G→V	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-10.44	chr19-58556132-C-A
234	G→V	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-10.44	COSV53396668
235	G→A	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.60)	-6.74	chr19-58556129-C-G
235	G→S	missense_variant	gnomAD	—	6.84e-07	—	ambiguous (0.45)	-5.80	chr19-58556130-C-T
235	G→V	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.93)	-7.87	COSV53397000
235	G→D	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.97)	-10.05	COSV53397761
236	Y→Y	synonymous_variant	gnomAD	—	9.58e-06	—	—	0.00	chr19-58556125-G-A
237	I→I	synonymous_variant	gnomAD	—	1.23e-05	—	—	0.00	chr19-58556122-G-A
237	I→M	missense_variant	gnomAD	—	2.74e-06	—	likely_benign (0.30)	-5.11	chr19-58556122-G-C
237	I→I	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-58556122-G-T
237	I→V	missense_variant	gnomAD	—	6.85e-06	—	likely_benign (0.06)	-0.06	chr19-58556124-T-C
237	I→V	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.06)	-0.06	ClinVar:4601252
238	G→A	missense_variant	gnomAD	—	2.05e-06	—	ambiguous (0.47)	-7.12	chr19-58556120-C-G
238	G→S	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.31)	-5.56	chr19-58556121-C-T
238	G→D	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.76)	-7.22	COSV99448418
239	S→C	missense_variant	COSMIC	—	—	damaging	likely_benign (0.20)	-9.38	COSV99448201
240	T→N	missense_variant	gnomAD	—	2.74e-06	—	likely_benign (0.15)	-5.77	chr19-58556114-G-T
240	T→P	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.86)	-12.71	COSV99447856
242	F→F	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-58556107-A-G
243	E→D	missense_variant	gnomAD	—	3.43e-06	—	likely_benign (0.08)	-4.14	chr19-58556104-C-G
243	E→E	synonymous_variant	gnomAD	—	2.06e-06	—	—	0.00	chr19-58556104-C-T
244	R→H	missense_variant	gnomAD	—	2.06e-06	—	ambiguous (0.38)	-7.50	chr19-58556102-C-T
244	R→C	missense_variant	gnomAD	—	6.86e-07	damaging	likely_pathogenic (0.60)	-8.18	chr19-58556103-G-A
244	R→C	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.60)	-8.18	COSV99448464
246	L→L	synonymous_variant	gnomAD	—	1.72e-05	—	—	0.00	chr19-58556095-C-G
247	K→R	missense_variant	gnomAD	—	6.87e-07	—	likely_benign (0.06)	-5.43	chr19-58556093-T-C
247	K→E	missense_variant	gnomAD	—	6.87e-07	damaging	ambiguous (0.38)	-8.87	chr19-58556094-T-C
247	K→N	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.67)	-7.02	COSV53397039

328 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.

UBE2M · ENST00000253023.8

Folding

Evidence — click any tile for the differential-region detail

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Details

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Elements and coordinates

Below threshold

Comparison

Comparison

Part 1 · Global feature comparison

Isoform-only features — 158 total (prevalence ≥ 2)

Canonical-only features — 36 total (prevalence ≥ 2)

Shared features by |Δ| activation — 1008 total (prevalence ≥ 2)

Part 2 · Differential coordinates

Unique-region features — 278 distinct (prevalence ≥ 2)

Clinical variants

Differential region — N-terminal extension (isoform-unique)

Shared canonical core — sequence common to canonical and isoform; AlphaMissense applies here