CDC34 · ENST00000215574.9

TRUNCATED 157 aa (canonical 236 aa) · UniProt P49427 · CDLMPS

chr19:535896:+:AAG:ENST00000215574.9

AI summary Truncation deletes the N-terminal third of the UBC catalytic fold, including a helix and three beta-strands that dock onto the retained core.

How it diverges

This truncation removes canonical residues 1-80, which structurally comprise a confidently-folded helix (8-22) and three beta-strands that make concentrated, non-random contacts with the retained core (hot spots at residues 90-97 and 169-193) — this is part of the load-bearing UBC catalytic-core architecture (IPR000608/IPR016135), not a disordered appendage. The large shared-region RMSD (8.23 Å) is not trustworthy as evidence of core refolding given low isoform pTM (0.63 vs 0.80 canonical), but the loss of this docked N-terminal substructure itself is a clear structural finding, reinforced by a large SAE feature shift (13.0, exceeding the UBC/UEV interface feature) consistent with loss of catalytic-domain architecture.

Why it matters

CDC34 is an E2 ubiquitin-conjugating enzyme whose catalytic core (built around active-site Cys95, contained in the retained C-terminal region) requires a properly folded UBC domain to charge with ubiquitin and transfer it processively to SCF-bound substrates; removing structured, core-contacting N-terminal secondary structure elements plausibly destabilizes or reorganizes the catalytic fold surrounding this active site, which could impair ubiquitin transfer even though the catalytic cysteine itself is retained. The DeepLoc-predicted ER addition is not a credible localization conflict — both canonical and isoform calls hover near identical, borderline confidence with unchanged NES/solubility signals — so it does not bear on CDC34's known nuclear/cytosolic/cytoskeletal localization.

Truncated functional regionInterpretable-feature shift

LLM confidence medium

The shared-region RMSD (8.23 Å) is not used as a Core refold claim due to low pTM; disease-variant density and germline constraint in the removed region are unremarkable (not enriched), tempering confidence that this loss is clinically consequential despite the structural plausibility.

Folding

Canonical (236 aa)

Download CIF

Isoform (157 aa)

Download CIF

Coloured by ESMFold2 pLDDT confidence (blue = high, orange/red = low). Differential region — residues 1–80 (lost from canonical) — recoloured on a yellow→purple pLDDT ramp so it stands out. Drag to rotate · scroll to zoom · download a CIF to explore in your own viewer.

Canonical PAE

Isoform PAE

Predicted aligned error: expected Cα error (Å) at residue j when the fold is superposed on residue i. Dark = confident relative placement; bright = uncertain. The dashed outline marks the differential region (1–80).

Evidence — click any tile for the differential-region detail

C Conservation Interesting

LLM reasoning

The N-terminal segment of canonical CDC34 that this truncation removes is under strong purifying selection, arguing its loss is likely to be functionally consequential rather than neutral. Primate amino-acid identity across the region is 99.4% (essentially matching the canonical baseline of 98.1%), mammalian identity is 99.7% (again above the canonical baseline of 96.6%), and absolute phyloP over the unique region is 4.77, well above the ~2 threshold for strong constraint and even somewhat higher than the shared-region mean of 3.93. All three conservation signals converge cleanly on high constraint, with no discordance to weigh.

Unique region 99.4% similar across primates

Conservation metric	Canonical ORF	Differential ORF
Mean AA identity	98%	99%
Frame intact (fraction of species)	76%	80%
Species aligned	25	25
Species frame-intact	19	20
Start codon conserved	96%	96%
Deepest intact species	Microcebus_murinus	Microcebus_murinus
Phylo depth (MRCA)	7	7

Unique region 99.7% similar across mammals

Conservation metric	Canonical ORF	Differential ORF
Mean AA identity	97%	100%
Frame intact (fraction of species)	37%	84%
Species aligned	19	19
Species frame-intact	7	16
Start codon conserved	100%	100%
Deepest intact species	Loxodonta_africana	Loxodonta_africana
Phylo depth (MRCA)	12	12

Unique region PhyloP: 4.77 — purifying selection

Track	Differential	Shared	vs shared
phyloP mean	4.77	3.93	1.21
phastCons mean	0.837	0.835	—

Property	Canonical	Isoform
Start codon	ATG	AAG
Kozak context (−9..+4)	GCCGCCGCCATGG	TTCCTGACCAAGA
phyloP at start codon	5.69	7.06
phastCons at start codon	1	1
phyloP over Kozak window	4.32	5.77
phastCons over Kozak window	0.351	0.998
Kozak mismatch — full consensus	0	7
Kozak window GC content	0.846	0.462

D Detection Neutral

LLM reasoning

This alt TIS has genuine but thin ribosome-profiling support and no direct peptide confirmation, so detection is plausible but not robust. It is only seen in 1 of 6 cell lines (HeLa), though that one line shows a highly significant signal (Fisher q=1.6e-4, ribo p=7.5e-6) with initiation efficiency 0.036, about half the canonical start's efficiency in the same line (0.071) and well below canonical efficiency in the other five lines (0.04-0.18) where the alt TIS wasn't called at all. Since this is a truncation, the differential region is the N-terminal segment of the canonical protein that gets removed, not a novel unique sequence, so there is no isoform-unique peptide space to validate; the mass-spec check accordingly reports 0/0 unique peptides, which is uninformative rather than a negative finding. Overall the evidence is limited to a single reproducible but modest-efficiency ribo-seq signal, insufficient to call this category a strong positive or negative.

detected in 1/6 cell lines

Cell line	Canonical	Isoform	p-value
HeLa	4.01	2.01	0.00016
K562	26.2	—	—
U2OS	4.35	—	—
RPE1 Async	2.44	—	—
RPE1 Que	2.89	—	—
RPE1 Sen	2.72	—	—

alt used 0.5× vs canonical

Cell line	Canonical	Isoform
HeLa	0.0714	0.0357
K562	0.179	—
U2OS	0.0794	—
RPE1 Async	0.0422	—
RPE1 Que	0.0646	—
RPE1 Sen	0.0433	—

0/0 isoform-unique peptides validated

Feature	Canonical	Isoform
Tryptic peptides (in-silico)	21	0
Validated by mass-spec	0	0
Isoform-unique peptides	—	0

L Localization Neutral

LLM reasoning

The DeepLoc compartment call gains an added endoplasmic-reticulum prediction on top of the shared cytoplasm/nucleus call, but this is a weak signal: the isoform's top-class probability (0.71) is barely above and even slightly lower than canonical's (0.73), the ER probability shift is modest (0.62 to 0.71), and nuclear-export-signal and membrane-solubility calls are both unchanged (soluble, NES retained in both). No bona fide sorting signal was gained or lost — SignalP and TargetP predictions are identical between isoform and canonical (both OTHER/noTP, probability deltas near zero), meaning there is no evidence of a new secretory or organellar targeting signal. Given the truncation only removes an N-terminal stretch, this pattern looks more like borderline probabilistic noise in a multi-label classifier than a genuine relocalization event.

iso: Cytoplasm, Nucleus, Endoplasmic reticulum | canon: Cytoplasm, Nucleus

Property	Canonical	Isoform
Predicted location	Cytoplasm\|Nucleus	Cytoplasm\|Nucleus\|Endoplasmic reticulum
Sorting signals	Nuclear export signal	Nuclear export signal
Membrane	Soluble	Soluble

iso: noTP | canon: noTP

Predictor	Canonical	Isoform
TargetP	noTP	noTP
SignalP	OTHER	OTHER

M Mutation Landscape Not interesting

LLM reasoning

Every axis argues against a meaningful mutation-landscape signal in this truncation's removed N-terminal segment (canonical residues ~0-78). Disease-variant density is depleted rather than enriched in the unique region (enrichment ratio 0.64, 35 vs 108 variants), and none of the 8 ClinVar entries there carry a pathogenic call — all are "Uncertain significance," matching the pre-computed n_pathogenic_unique=0. Positional clustering is diffuse: 191 variants spread across 70 distinct positions with only 30.4% falling on the ten busiest residues and no position exceeding count 8, i.e. no hotspot. Germline constraint signals are weak/contradictory on their own terms (ESM-C constraint_enrichment 0.10, gnomAD depletion ratio 0.87, both far from decisive), and per-variant effect scores in the unique region (mean AlphaMissense 0.53, 89/191 flagged damaging) are essentially indistinguishable from the shared retained core (mean 0.52, 210/465 damaging) — so the removed segment shows no distinctive damaging-variant burden compared to the rest of the protein. Together this is a consistent negative result, not a case of conflicting evidence.

gnomAD variants 1.15× less in unique region — constrained

Variant set	Differential	Shared	Depletion ratio
gnomAD variants	156	357	0.87×

Property	Differential	Shared	Enrichment
ESM-C mean LLR	-0.00497	-0.0495	—
Constrained positions	0	0	—

Variant set	Differential	Shared	Enrichment
Scorable variants	156	345	0.89×
Damaging variants	73	150	0.96×
— of which loss-of-function	10	20	0.98×
AlphaMissense-pathogenic	38	87	0.86×

Property	Differential	Shared
Mean ΔLLR (ESM-C)	-5.18	-5.22
Min ΔLLR (ESM-C)	-13.9	-15.5
Mean AlphaMissense	0.527	0.499

Disease variants 1.55× less in unique region — depleted

Variant set	Differential	Shared	Enrichment
Disease variants	35	108	0.64×
Pathogenic	0	0	—

Variant set	Differential	Shared	Enrichment
Scorable variants	35	105	0.65×
Damaging variants	16	60	0.52×
— of which loss-of-function	1	0	—
AlphaMissense-pathogenic	11	40	0.54×

Property	Differential	Shared
Mean ΔLLR (ESM-C)	-6.17	-6.83
Min ΔLLR (ESM-C)	-12.7	-14.8
Mean AlphaMissense	0.542	0.577

P Predicted Structure Interesting

LLM reasoning

The truncation removes canonical residues 1-80, which contain multiple confidently folded secondary-structure elements (a 15-aa helix at residues 8-22, pLDDT 0.92; three strands at 40-45, 56-64, 71-77, pLDDT 0.93-0.97) that are confidently placed against the retained core (PAE to the body ~8.4-8.5 Å) and make concentrated, non-random contacts with specific shared-core patches (45 residues contacted, hot spots at 90-97 and 169-193, up to 5 contacts each). This is a genuine load-bearing element being deleted, not a disordered appendage. The shared-region RMSD of 8.23 Å is large but should not be read as evidence of core refolding: isoform pTM is only 0.627 versus 0.804 for canonical, so the qualifier gate argues this is placement uncertainty in a lower-confidence model rather than a real conformational change; the global RMSD is much smaller (1.45 Å), reinforcing that most of the discrepancy is confined to how the shared region is superposed, not a wholesale reorganization. The dominant, trustworthy signal is the loss of well-folded, well-docked secondary structure from the truncated N-terminus.

pLDDT Differential Region: 0.92

Metric	Canonical	Isoform
pLDDT (whole protein)	0.899	0.851

Metric	Differential	Shared	Enrichment
pLDDT	0.92	0.957	0.96

Shared-Region RMSD: 8.23 Å

Property	Canonical	Isoform
Shared-region pLDDT	0.888	0.852

4 secondary structures identified in unique region

Metric	Differential	Shared
Alpha helices	1	3
Beta strands	3	1
Longest element (aa)	15	20
Mean pLDDT	0.96	0.93

Removed (canonical)	Shared core
alpha helix 8–22 15 aa · pLDDT 0.92	alpha helix 120–132 13 aa · pLDDT 0.94
beta strand 40–45 6 aa · pLDDT 0.97	alpha helix 142–154 13 aa · pLDDT 0.97
beta strand 56–64 9 aa · pLDDT 0.96	alpha helix 160–179 20 aa · pLDDT 0.95
beta strand 71–77 7 aa · pLDDT 0.97	beta strand 220–232 13 aa · pLDDT 0.84

Removed (canonical)	Shared core
beta strand 28–32 5 aa · pLDDT 0.94	—

S Structural Characteristics Interesting

LLM reasoning

This truncation removes the N-terminal segment of canonical CDC34, and the strongest signal is that this deletion eliminates real, annotated catalytic domain architecture: the removed region overlaps the ubiquitin-conjugating (UBC) core domain identified by multiple InterPro-linked databases (PROSITE, SUPERFAMILY, PANTHER, SMART, CDD, Pfam), even though the domain-change submodule itself reports zero domains fully contained within the differential region boundary (likely because the domain spans both removed and retained sequence). The whole-protein biophysical shift did not cross threshold on any single descriptor (gravy delta -0.16, fraction-charged delta +0.03, disorder delta +0.02), so no strong global physicochemical change is indicated. However, the sparse-autoencoder magnitude check does fire: the strongest shared-feature activation shift reaches 13.02, above the 10.0 threshold, indicating a substantial change in a learned protein-level feature between isoform and canonical, consistent with loss of the folded catalytic core rather than a superficial sequence change. Taken together, the domain evidence and the magnitude-significant feature shift argue this truncation is structurally consequential, disrupting the enzyme's catalytic architecture even though bulk biophysical properties remain largely unchanged.

No diverging domains

Feature	Canonical	Isoform
InterPro domains	10	9
Short linear motifs	2	2

more hydrophobic (+0.52) · less charged (-0.09) · less disordered (-0.05)

Property	Differential	Shared	Enrichment
Isoelectric point (pI)	4.98	3.95	1.26
Hydropathy (GRAVY)	-0.26	-0.776	0.335
Fraction charged	0.237	0.331	0.717
Disorder fraction	0.101	0.153	0.658
Disorder-promoting	0.55	0.586	0.939
Low-complexity fraction	0	0.159	0
Prion-like fraction	0.237	0.236	1.01
LLPS score	0.156	0.169	0.923
π–π propensity	0.263	0.191	1.37
Aromaticity	0.163	0.0828	1.96
Instability index	46.2	51.7	0.893
Shannon entropy	3.93	4.09	0.962
Normalized complexity	0.91	0.946	0.962

429 SAE features differ

Feature	Label	Description	Activation	Prevalence
#512	Short functional domain segments	Short sequence segments distributed across diverse proteins, with peaks that often fall within structured catalytic, transporter, or fold-defining domains as well as occasional acidic/charged stretches and flexible linkers.	6.51	14
#1460	Hydrophobic helix-helix interfaces	Hydrophobic faces of stable alpha-helices that mediate helix–helix packing (coiled‑coils and helical‑bundle cores), rather than specific catalytic or metal‑binding sites.	2.86	2
#4632	Regulatory all-alpha helical bundles	Structured all‑alpha helical bundle cores of eukaryotic regulatory proteins—the amphipathic-helix surfaces that scaffold partner/ligand binding—most prominently the cyclin box of cyclins, but also analogous helical regulatory folds (nuclear receptor ligand‑binding domains, ENTH domains, and the central helical region of ORC6), spanning cell‑cycle and transcriptional regulators.	2.45	13
#15846	SH2 domain fold recognition	Canonical SH2 domain fold (and close SH2-like variants), capturing the central antiparallel β-sheet with flanking helices that mediates binding to phosphorylated peptide motifs (classically pTyr), as found across eukaryotic signaling and transcriptional regulators; additionally, the feature can weakly recognize noncanonical β-sheet–rich modules with similar aromatic/Gly composition in some transcription factors/cofactors (e.g., TFIIF-α).	2.26	3
#8838	P450 heme-binding Cys pocket	Cytochrome P450 heme-binding Cys-pocket and its upstream “meander” loop—i.e., the conserved C‑terminal heme‑ligand region including and immediately preceding the FGxGxxxCxG signature that carries the axial heme‑coordinating cysteine; a fold-level element shared across diverse P450 families and taxa	2.24	4
#16105	Helical hydrophobic/basic motif	Conserved residue-level feature that fires on hydrophobic and basic residues (Val/Leu/Ile/Phe/Arg) embedded in alpha-helical segments of bacterial and eukaryotic enzymes, frequently within or adjacent to nucleotide-binding/catalytic domains but not on the catalytic residues themselves	2.23	2
#15710	Hydrophobic catalytic pocket flanks	Hydrophobic scaffold residues that line and stabilize catalytic clefts of nucleotide/cofactor- and metal-assisted chemistry—most prominently the two‑metal sites of RNase H–like/Toprim nucleic‑acid enzymes (reverse transcriptase, RNase H, DDE integrase)—and analogous nucleotide/cofactor pockets (ATP/Mg2+, CoA, SAM) in PPTases, aminoacyl‑tRNA synthetases, and DNA/RNA methyltransferases; the feature also marks comparable active‑site clefts in other enzyme families while sparing disordered/noncatalytic regions.	2.17	2
#1018	Acidic sheet-edge caps	Acidic/polar residues at beta‑strand termini and the immediately following turn/coil (beta‑hairpin/strand‑to‑loop junction), i.e., sheet‑edge/capping positions enriched for Asp/Asn/Glu and often flanked by Gly/Pro; a general structural motif rather than an active‑site signal	2.17	2
#10654	Catalytic core hydrophobic packing	Hydrophobic, aliphatic-rich segments within the catalytic cores of thiolase-fold condensing enzymes and related soluble enzymes, marking buried packing helices/strands around the active-site region.	2.16	2
#3357	Surface acidic-aromatic patch	A regional feature marking surface-exposed Pro/aromatic-rich acidic patches in secreted/extracellular proteins and certain soluble enzymes, often distinct from but in the same domain as conserved catalytic motifs; occasionally extending into flexible linkers connecting domains.	2.16	2
#9812	Non-catalytic beta/coil edge patches	Short, surface-exposed β-strand/loop "edge" segments at domain boundaries and coil↔β transitions, typically on non-catalytic surfaces. These patches are common in extracellular/secreted proteins (glycan-active enzymes, metalloproteases, lysosomal glycoproteins, cytokines) but also occur in intracellular nucleic-acid proteins, where they act as recognition/hinge/linker elements and can include N-glycosylation- or propeptide/linker regions.	2.14	2
#1115	Amino acid kinase hydrophobic motif	Conserved hydrophobic motif within the amino-acid kinase family (UMP kinase / glutamate-5-kinase fold), located on a helix adjacent to the substrate-binding pocket.	2.09	2
#7348	Secreted cysteine-crosslinked peptide detector	Residue-level detector for small secreted cysteine-rich bioactive peptides (lantibiotics, toxins, antimicrobial peptides) and disordered segments of secreted preproproteins; it frequently fires on or immediately adjacent to cysteines that participate in disulfide bonds or lanthionine/methyllanthionine crosslinks.	2.07	2
#13969	Helix-start N-cap residues	Alpha-helix N-cap/helix-initiation sites: residues at or immediately preceding the first helical turn (N′/Ncap/N1) that mark coil-to-helix transitions and cap/stabilize helix starts, typically enriched in charged/polar and helix-modulating residues (D/E/K/R with Y/P/G)	2.05	3
#371	Charged low-complexity helical regions	Charged, low-complexity eukaryotic segments that initiate or comprise alpha-helical interaction-prone regions (e.g., coiled-coils or helical repeats) and/or their flanking linkers, enriched in acidic/basic and serine residues and commonly serving as activation/linker/oligomerization modules.	2.01	6
#12266	Glycine-rich strand-capping loop	A short small-residue-rich strand-capping loop motif at beta-strand termini—typically at beta→alpha or beta→beta junctions—corresponding to classic glycine loops for phosphate/cofactor binding or tight active-site turns across diverse protein families.	1.97	2
#2840	Phage tailspike depolymerases	Phage tail spike and capsule depolymerase proteins, with activation concentrated within the parallel beta-helix/depolymerase fold used to recognize and cleave host capsular polysaccharides.	1.92	2
#14791	PH-domain phosphoinositide binding	Pleckstrin homology (PH) and PH-like lipid-binding β-sandwich modules—including canonical PH domains and PH-like insertions (e.g., FERM-PH) or noncanonical PH-like membrane-association modules in large Arf-GEFs—that form phosphoinositide-binding surfaces for membrane recruitment in diverse signaling and trafficking proteins.	1.88	2
#1147	Metal-dependent hydrolase and transport motifs	Metal/cofactor- and membrane transport-associated sequence elements: the feature highlights metal-dependent hydrolase active-site regions (dominantly PP2C/PPM Ser/Thr phosphatases; occasional PTPs; secreted esterases/deacetylases and some Ca2+-binding glycosidases), membrane channel/transport motifs (Amt/Rh ammonium channels, CTR copper transporters, and some outer-membrane porins/efflux factors), with broader activation across low-complexity/coiled-coil linkers in large nucleic-acid-associated proteins (e.g., retroelement Pol and some chromosome-partition proteins) and small metal-cofactor assembly factors.	1.87	2
#13232	Short extracellular surface loops	Short surface loops in extracellular/exposed regions of membrane-associated and secreted proteins, with the dominant signal on a conserved β-hairpin/loop in bacterial outer-membrane omptin-family aspartyl proteases.	1.84	2
#8676	Transmembrane helix interface signature	Residue-level signature of transmembrane α-helix interfaces in integral membrane proteins (single- and multi-pass), highlighting helix termini and kink/anchor positions (aromatic “belt” residues and Gly/Pro-mediated kinks) and nearby TM–loop boundaries rather than catalytic sites	1.83	3
#6416	Viral capsid beta-sandwich core	Long contiguous activation patches within structured β-sandwich/jelly-roll domains, prominently in viral capsid proteins and related fold-rich segments, with peaks landing on residues inside β-strand/turn elements of the structured core.	1.72	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	1.70	2
#7552	Acidic IDR transactivation regions	Intrinsically disordered, low‑complexity partner‑recruitment/activation regions of DNA‑associated regulators—acidic/proline/serine‑rich IDRs that function as transactivation or cofactor‑recruiting tails, typically long C‑terminal segments (with occasional N‑terminal regulatory IDRs), harboring coactivator‑binding SLiMs and Pro‑directed phosphorylation motifs; predominantly in transcription factors/coactivators, but also present in some viral DNA replication initiators/helicases that recruit host factors.	1.66	2
#7258	Membrane flanking low complexity IDRs	Long, low‑complexity, intrinsically disordered segments—often terminal tails (especially C‑terminal) or internal linkers/loops—enriched in Gly/Pro and polar/charged residues (acidic or basic), most often flanking transmembrane/envelope proteins (insertases, translocase subunits, cell‑wall/secretory and respiratory membrane enzymes), but also present in other proteins; typically repeat‑rich and compositionally biased IDRs rather than structured domains.	1.63	2
#11475	Secreted protein C-terminus activation	Short contiguous C‑terminal segments of mature secreted, periplasmic, and outer‑membrane/surface‑exposed bacterial proteins, including lipoproteins, curli/amyloid fibril subunits, outer surface proteins, and periplasmic chaperone/assembly factors—activation lies in the mature chain and avoids the N‑terminal signal peptide.	1.62	3
#556	Membrane helix boundary recognition	Juxtamembrane/membrane–water interface recognition: residues at the starts/ends of membrane-spanning helices or membrane-interacting amphipathic/interfacial helices (helix caps at the membrane interface), rather than the hydrophobic helix core, across membrane-integral and membrane-associated proteins	1.59	2
#9899	Arrestin regulatory IDR motifs	Intrinsically disordered, low‑complexity Ser/Thr/Pro–enriched regulatory regions of arrestins/alpha‑arrestins and related eukaryotic membrane‑trafficking/signaling proteins; these tails/loops harbor short linear motifs (e.g., AP‑2/clathrin boxes, PY motifs, basic Lys clusters) and phospho‑sites used to recruit endocytic, ubiquitin‑ligase, and signaling partners, while the structured arrestin fold and other globular domains are largely not selected.	1.56	3
#4956	Alternating hydrophobic beta-strand face	Recognition of one face of beta-strands—an alternating side‑chain pattern enriched in hydrophobic/small residues—across beta-sheet/beta-barrel architectures, commonly forming lipid-interacting surfaces in membrane, lipoprotein, and pore-forming proteins	1.46	3
#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	1.45	2

Feature	Label	Description	Activation	Prevalence
#6441	Beta-strand core recognizer	Residue-level recognition of well-ordered beta-strand positions that form the cores of beta-sheet–rich folds across diverse proteins (Ig-like beta-sandwiches, beta-propellers, arrestin-like, F-box associated/FBA, ML/MD-2, and beta-strand enzymes); in secreted/Ig-like contexts the peaks often lie next to disulfide-bonded cysteines and frequently coincide with or flank N-glycosylation sequons.	10.63	5
#3904	Beta-strand residue signal	Beta-strand secondary-structure signal: the feature marks residues within ordered β-sheets (DSSP class E), often in extracellular/luminal domains but broadly across taxa and functions; enrichment for polar/charged side chains within strands rather than specific catalytic motifs	9.76	6
#1029	Fe2OG dioxygenase catalytic core	A feature marking conserved structured positions in the Fe2OG dioxygenase fold of plant 2-oxoglutarate/Fe(II)-dependent oxygenases, with peaks clustered in the catalytic domain and one peak typically falling directly on the Fe-coordinating histidine.	9.59	4
#15220	Beta-strand residue signal	Generic structural signal for residues positioned in beta-strands (and adjacent well‑ordered loops) of globular domains, with a slight bias toward small polar/charged residues; broadly taxonomic and functional, often near—but not at—ligand/metal/catalytic motifs	9.06	5
#6843	Ordered nonfunctional residue detector	Sparse detector that fires on isolated residues in structured regions of soluble and membrane proteins, avoiding intrinsically disordered regions and annotated catalytic/ligand-binding sites; recurrently activates on a conserved "EIRA[S/G].LSGEC"-like motif in mitochondrial inner membrane protease ATP23 orthologs	9.00	3
#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	8.84	4
#6819	Proline-anchored strand-loop boundaries	Proline-anchored loop/turn motifs at beta-strand termini and strand–loop–strand connectors (often in P/Ser/Thr/Gly-rich segments), marking boundaries between ordered beta structure and coil/disorder and recurring in beta-rich/repeat architectures (e.g., LRR, beta-propeller) as well as soluble beta-grasp–like folds	8.77	6
#6377	Interface-adjacent conserved motifs	A "functional-site adjacency" signal that fires at residues within well-ordered secondary structure participating in, or immediately flanking, ligand/cofactor-binding, catalytic, or protein-protein interaction interfaces, with a particularly strong pattern at conserved motif residues of small interaction modules (CCT, SOCS-box, BC-box).	8.44	4
#8805	Exposed loops/termini CBX-enriched	Microfeature firing on isolated, mostly solvent-exposed residues in coils, turns, and at the ends of secondary structures, often near domain boundaries or in terminal tails, and not tied to catalytic or cofactor-binding sites. Strongly enriched on Polycomb chromobox (CBX) family proteins, where it picks up a conserved C-terminal region and a position within the Chromo domain.	8.36	6
#16214	Nontransmembrane beta strands/turns	A general secondary-structure signal for short beta-strands and their flanking turns/coil in non-transmembrane regions (extracellular or cytosolic), with a preference for small/flexible or polar/charged residues; strongly depleted in alpha-helices, especially membrane-spanning helices.	8.36	4
#14447	Secondary structure capping residues	Residues that cap or initiate secondary‑structure elements—especially helix N‑caps/first helical turns and β‑strand termini/adjacent turns—across many folds; frequently realized in structured propeptides and extracellular/periplasmic domains, but not tied to catalytic sites.	8.13	8
#14927	Structural and domain boundary residues	Residues at structural and domain junctions: starts/ends of secondary-structure elements (especially helix starts and transmembrane-helix termini) and positions immediately preceding or following annotated domains, often adjacent to ligand/cofactor-binding regions	7.94	4
#9192	Single residue secondary structure detector	Generic detector of isolated residues embedded in canonical secondary-structure elements (alpha-helices and beta-strands), including transmembrane and signal-peptide helices and coiled-coils; reflects local backbone order/packing rather than any specific functional motif.	7.86	4
#14744	Extracellular beta-strand hydrophobics	Hydrophobic residues positioned within well‑ordered β‑strands of β‑sheet architectures (e.g., β‑propellers, β‑sandwich/Ig‑like, and other β‑rich domains), especially in extracellular/periplasmic or lumenal portions of secreted and membrane‑associated proteins; the signal avoids helices, transmembrane segments, glycosylation/metal‑binding sites, and most disulfide‑anchored positions.	7.83	4
#1616	Helix N-cap boundary residues	Helix N-cap and loop-to-helix transition residues: single positions in short coil/turn segments that cap or immediately precede alpha helices (including transmembrane helices), enriched for Ser/Thr/Asp/Glu and often Pro/Gly typical of helix-capping motifs; a generic secondary-structure boundary signal rather than a family-specific functional site.	7.81	2
#15225	Beta-sheet core hydrophobes	Hydrophobic side chains in beta-strands (and immediately adjacent coils) of well‑ordered globular or extracellular domains, marking sheet‑core packing sites that scaffold nearby functional elements; strong preference for V/I/L/F/Y/A and avoidance of transmembrane helices and disordered segments	7.75	7
#10600	Hydrophobic beta-strand preference	Preference for hydrophobic residues (Leu/Val/Ile/Phe/Tyr/Met, also Ala) occupying beta‑strand positions in well‑ordered beta‑sheet regions across diverse proteins; a structural, not function‑specific, signal that favors aliphatic/aromatic and small hydrophobic side chains in beta‑strands while avoiding helices, transmembranes, signal peptides, and disordered segments.	7.61	6
#8085	OB-fold AEWGEG turn	A short conserved motif centered on an aromatic-glycine turn, matching an A-E-W-G-(E/Y)-G consensus that caps a β-strand and initiates a β→coil/helix transition in the C-terminal OB-fold-like region of ATP-dependent DNA ligases. The motif lies distal to catalytic and ATP-binding residues.	7.38	8
#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.	7.21	2
#94	Gly/Ser/Pro-rich junction loops	Short glycine/serine/proline–enriched coil/turn segments at secondary‑structure junctions (beta‑turns and helix‑capping loops), typically the small loops connecting strands or marking coil→helix/coil→strand transitions; a generic structural loop motif that recurs across diverse enzymes and repeat scaffolds and can lie adjacent to active sites.	7.07	12
#14958	Active-site motif-adjacent capping residues	Active-site–proximal helix/loop capping residues that flank conserved catalytic or ligand/cofactor– or nucleic‑acid/partner‑binding motifs (e.g., near metal‑binding, nucleotide‑/RNA‑binding, disulfide, or selectivity‑filter residues) across diverse proteins	7.05	2
#2088	Acidic glycine-rich loop motifs	Short local sequence motifs in turn/loop or strand contexts, including acidic and Gly-containing turns (e.g., DG/GD-bearing segments) as well as a recurrent LFxLT-centered patch, used as flexible elements across diverse proteins (e.g., loops in metabolic enzymes and short recognition segments in adaptor/binding proteins)	6.91	3
#16026	Solvent-exposed caps and linkers	A generic structural signal for short, solvent-exposed residues that cap or connect secondary-structure elements (β-turns, helix/strand caps, inter-repeat/linker hinges), typically falling on small or charged residues at flexible regions and avoiding catalytic, cofactor-binding, or metal-ligating sites.	6.80	6
#8964	Beta-strand capping motifs	β-structure capping elements: the feature marks β-strands and immediately adjacent strand–turn–helix junctions (β-edge/β→α motifs), i.e., β-hairpins and β-sheet edges often stabilized by glycine/proline and charged residues.	6.79	3
#15557	CBX/WRKY conserved motifs	Conserved short motifs within chromatin-associated reader/writer modules and plant zinc-finger DNA-binding domains; the feature highlights residues in the canonical chromodomain (Chromo) of CBX/Polycomb-family proteins together with conserved C-terminal motifs of those same proteins, and the WRKY DNA-binding domain of plant WRKY transcription factors.	6.79	5
#11290	Conserved TAFA/SELENOT motif residues	Conserved residue positions within two small secreted/membrane-associated protein families — the TAFA chemokine-like protein family and selenoprotein T — firing at homologous positions across paralogs and orthologs.	6.76	5
#1635	Glycine-rich flexible active-site loops	Glycine-centered flexibility sites: glycine (and occasionally other small residues) in loops/turns and at helix/strand junctions that form or flank catalytic and ligand/metal/nucleotide-binding motifs (glycine-rich loops such as P-loop/DFG, glycine clusters in cofactor-binding loops, and glycine positions adjacent to conserved catalytic residues) across diverse proteins.	6.75	5
#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.	6.57	12
#9883	Helical hydrophobic interface hotspot	Generic short alpha-helical hydrophobic face used as a protein–protein interaction/packing hotspot, with occasional recognition of adjacent loop/turn glycines at helix boundaries	6.52	3
#16352	Helix-start N-cap marker	Alpha-helix initiation and capping sites: residues at the N-terminus of helices and the immediately preceding strand/coil positions (N-cap/N′ and first helical turns), often enriched in small or flexible residues and gly/gly-rich pre-helix loops; highlights secondary-structure transition points rather than catalytic motifs	6.46	8

Feature	Label	Description	Δ activation	Iso act.	Canon act.	Iso prev.	Canon prev.
#1066	UBC/UEV HPN-loop interface	Strand-helix-loop interaction patch of compact alpha/beta domains, most prominently the UBC/UEV (ubiquitin-conjugating-like) fold where it captures the conserved HPN-loop and adjacent beta-strand/helix that form the partner-binding surface; secondarily, the feature recognizes geometrically analogous beta-strand–helix patches in other interaction/DNA-binding domains (e.g., T-box and EVH1-like).	-13.02	3.93	16.95	27	99
#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	-7.76	11.05	18.81	156	224
#13818	N-terminal domain start signal	Start-of-domain signal: the feature detects the transition into the first ordered secondary-structure elements at the N-terminus of a conserved globular domain (often immediately after a signal/transit peptide, lipidation site, or disordered tail), with strongest matches for cyclophilin-type PPIase folds and weaker matches for many other domain starts.	-5.89	2.48	8.37	64	117
#6141	Soluble/extracellular beta-strand junctions	Residues within structured soluble/extracellular domains, marking short stretches in beta-sheet-rich regions and adjacent coils, consistent with generic beta-structure preferences rather than a specific function.	-4.88	5.20	10.09	2	9
#12037	Proline-rich low-complexity regions	Proline-rich low-complexity regions (PRRs) characterized by polyproline motifs with interspersed Ser/Thr (± acidic) residues, including PXXP/PPXP sequences that adopt polyproline II conformations; these segments frequently function as intrinsically disordered linkers and include canonical SH3/EVH1-binding sites across diverse proteins.	-4.84	4.73	9.56	3	8
#1727	3-6 residue micro-motifs	Short 3-6 residue micro-motifs occurring within folded protein domains and occasionally in disordered/polar low-complexity stretches, often containing a mix of charged, polar, and aromatic residues together with Pro/Gly.	-4.38	2.50	6.88	2	26
#7095	N-terminal start-of-chain detector	N-terminal start-of-chain detector that recognizes signal peptides and the immediate post-cleavage beginning of the mature polypeptide, with strong emphasis on conserved N-terminal motifs of secreted, disulfide-rich peptides (e.g., paired/first cysteines in chemokines/defensins); more generally, it marks the extreme N-terminal tail/first helix across diverse proteins.	-4.38	1.28	5.66	4	23
#4485	Hydrophobic alpha-helical segments	Hydrophobic alpha-helical segments in soluble globular proteins, prominently a conserved helix near the active site of glycoside hydrolase family 27 alpha-galactosidases.	-4.09	8.34	12.42	72	117
#9207	Short β-strand edge motif	A generic short-segment signal for β-strand/edge and adjacent turn/coil regions: hydrophobic/aromatic- and proline-enriched 7–12-residue windows that either constitute a β-strand or lie immediately N- or C-terminal to one (often at domain boundaries or in flexible linkers), including segments just upstream of disulfide-forming cysteines in small secreted peptides.	-3.99	2.08	6.07	2	26
#5028	Beta-biased core hydrophobes	Generic preference for hydrophobic/aromatic residues in regular secondary structure cores—strongest in beta-strands but also present in alpha-helices—plus occasional recognition of short hydrophobic/proline-rich extended patches in disordered tails; not motif- or function-specific.	-3.98	1.90	5.89	2	9
#8337	Domain edge helix cap motifs	Short linear motifs at secondary-structure transitions and domain/linker junctions—helix caps and nearby loops/turns at the edges of structured domains—often enriched for Pro and aromatic residues (especially Trp) and composed of mixed basic and polar/hydrophobic residues; these segments frequently border or contribute to ligand/RNA-binding pockets	-3.21	3.26	6.47	4	34
#1911	Solvent-exposed beta-sheet edges	Solvent‑exposed residues in well‑ordered β‑strands and their adjoining turns, especially edge/terminal strands of β‑sheets in β‑sandwich or α/β enzyme cores (often in extracellular/periplasmic/ER‑lumenal domains and near β‑sheet→TM junctions), enriched for acidic/hydroxyl residues with frequent Gly/Pro and occasional aromatics.	-3.16	4.85	8.01	5	9
#3639	Electrostatic surface loop patches	Short, charged/polar surface micro-motifs in flexible loops or helix N‑caps (enriched in G/S/T with K/R and/or D/E; often resembling G–E/A–A–T–K/E), forming electrostatic patches used for nucleic‑acid or phosphate binding and for docking to acidic/basic protein partners; a generic interaction/catalytic-site‑adjacent motif rather than a family-specific signature	-3.02	3.13	6.15	4	15
#2433	N-terminal short motif detector	A short linear-motif detector with a strong N‑terminal bias: it highlights contiguous 3–10 aa patches in the mature chain just downstream of any signal/transit cleavage site, often in polar/charged or low-complexity stretches.	-2.85	2.71	5.56	3	24
#2972	Beta-strand loop connectors	Short, ordered beta-strand–loop transition motifs (beta-turn/hairpin connectors) at the ends of beta-strands within beta-rich domains, typically enriched in acidic/polar residues and glycine/proline; a broad, structural signal rather than a function-specific motif	-2.79	3.60	6.39	4	11
#7486	Generic alpha-helical scaffold signal	Generic alpha-helical scaffold signal: the feature marks short internal stretches of well-ordered alpha helices and adjacent helix–loop junctions across diverse proteins, especially in all‑alpha/alpha‑repeat domains (e.g., cyclin box, PUF repeats) and also in transmembrane helices; it reflects structural packing/architecture rather than catalytic or ligand-binding motifs.	-2.76	1.88	4.63	2	6
#6858	Conserved micro-motif detector	Sparse, context-dependent feature that fires on short conserved sequence patches in small/medium proteins, with peaks typically falling on a single residue or a brief loop rather than on catalytic or cofactor-binding sites.	-2.64	2.26	4.90	5	20
#9902	Mixed-charge beta-edge loops	Short motifs at beta-sheet boundaries (strand edges and adjacent turn/loop linkers), highlighting positions that include both charged (Lys/Arg/Asp/Glu) and hydrophobic/aromatic residues; a broad, structure-level signal rather than a specific function.	-2.51	3.21	5.72	2	5
#11421	Hydrophobic/aromatic core packing	Broad hydrophobic/π-residue packing in well-ordered secondary structure, concentrated in the buried cores of folded domains; preferentially highlights Tyr/Phe/Trp/His and aliphatic Leu/Ile/Val, and often includes Cys in disulfide-stabilized secreted/lectin folds	-2.26	3.01	5.27	20	28
#6479	Acidic hydrophobic beta-strand motif	Short beta-strand micro-motifs enriched in acidic (Asp/Glu) and hydrophobic residues (often including Tyr), occurring within diverse beta-sheet–containing domains and at strand–loop junctions; a generic structural signal rather than a family-specific active-site motif	-2.19	1.89	4.09	2	5
#15214	Beta-alpha junction N-cap motif	A generic structural motif: the beta-strand to alpha-helix junction (helix N-cap/capping-box) characterized by a short loop/turn followed by the first residues of an alpha-helix, enriched in acidic and small/polar residues (E/D/S/T/G) and sometimes containing Pro or Trp.	-2.17	2.50	4.66	2	6
#6384	Widespread activation in folded proteins	Proteins showing broad, diffuse activation across large fractions of their sequence, with peaks frequently occurring in folded regions of single-domain or multi-domain enzymes and structural proteins.	+1.94	3.96	2.02	10	23
#194	Edge-of-sheet patches	A generic structural micro-feature: short beta-strand segments and immediately adjacent strand–loop junctions (“edge-of-sheet” elements) within beta-sheet–containing domains, often forming small interface/assembly patches rather than catalytic motifs; recurrent across many protein families and taxa, with frequent Gly and Lys/Arg (and often Pro) in the activated windows.	-1.94	2.93	4.88	4	6
#5549	Soluble β-strand/turn motifs	Short structured motifs (≈2–6 residues) in soluble domains, most often β-strand/turn elements in β-rich folds (β-sandwich/all-β) of extracellular/lumenal or periplasmic/IMS proteins, and also in adjacent loop or short-helix segments of other soluble folds; includes N-terminal edge strands of Ig-like domains and analogous short motifs in diverse folds.	-1.91	2.13	4.05	2	11
#5335	SEA domain autoproteolysis serine	Serine-centered feature that detects a conserved isolated serine within SEA (sea urchin sperm protein/enterokinase/agrin) domains of extracellular/membrane-anchored proteins, typically in the context S-S-x-Y-Q-E or similar around the SEA autoproteolysis loop; also fires on isolated solvent-exposed serines in short loops of other secreted/GPI-anchored proteins	-1.58	2.14	3.72	2	4
#1803	Unknown generic feature	Unknown generic feature	-5.58	10.39	15.97	155	234
#14895	Unknown generic feature	Unknown generic feature	-5.39	18.36	23.75	157	236
#14534	Unknown generic feature	Unknown generic feature	-2.94	12.63	15.57	155	233
#9005	Unknown generic feature	Unknown generic feature	-2.46	9.05	11.52	115	189
#9214	Unknown generic feature	Unknown generic feature	-2.00	16.33	18.33	157	236

Feature	Label	Description	Activation	Prevalence
#2503	UBC/E2-like interaction domains	Compact α/β protein–protein interaction domains typified by the UBC (ubiquitin‑conjugating E2) fold and its E2‑like variants (UEV, RWD), with spillover to structurally analogous reader modules (e.g., YEATS); the feature highlights the structured core that mediates ubiquitin/UBL conjugation or partner/ligand recognition rather than disordered or coiled regions.	20.53	76
#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	18.81	69
#1066	UBC/UEV HPN-loop interface	Strand-helix-loop interaction patch of compact alpha/beta domains, most prominently the UBC/UEV (ubiquitin-conjugating-like) fold where it captures the conserved HPN-loop and adjacent beta-strand/helix that form the partner-binding surface; secondarily, the feature recognizes geometrically analogous beta-strand–helix patches in other interaction/DNA-binding domains (e.g., T-box and EVH1-like).	16.95	78
#4485	Hydrophobic alpha-helical segments	Hydrophobic alpha-helical segments in soluble globular proteins, prominently a conserved helix near the active site of glycoside hydrolase family 27 alpha-galactosidases.	12.42	46
#6441	Beta-strand core recognizer	Residue-level recognition of well-ordered beta-strand positions that form the cores of beta-sheet–rich folds across diverse proteins (Ig-like beta-sandwiches, beta-propellers, arrestin-like, F-box associated/FBA, ML/MD-2, and beta-strand enzymes); in secreted/Ig-like contexts the peaks often lie next to disulfide-bonded cysteines and frequently coincide with or flank N-glycosylation sequons.	10.63	4
#6141	Soluble/extracellular beta-strand junctions	Residues within structured soluble/extracellular domains, marking short stretches in beta-sheet-rich regions and adjacent coils, consistent with generic beta-structure preferences rather than a specific function.	10.09	7
#3904	Beta-strand residue signal	Beta-strand secondary-structure signal: the feature marks residues within ordered β-sheets (DSSP class E), often in extracellular/luminal domains but broadly across taxa and functions; enrichment for polar/charged side chains within strands rather than specific catalytic motifs	9.76	5
#12037	Proline-rich low-complexity regions	Proline-rich low-complexity regions (PRRs) characterized by polyproline motifs with interspersed Ser/Thr (± acidic) residues, including PXXP/PPXP sequences that adopt polyproline II conformations; these segments frequently function as intrinsically disordered linkers and include canonical SH3/EVH1-binding sites across diverse proteins.	9.56	5
#9354	Secondary structure boundary motif	Generic structural motif at secondary-structure boundaries (strand ends, short helices, and connecting turns); a broad, structure-level signal rather than a specific function, with peaks typically on hydrophobic or charged residues at strand/helix edges.	9.31	8
#1265	Aromatic hydrophobic hotspots	Generic detector of bulky aromatic hydrophobic side chains—especially tryptophan, tyrosine, and phenylalanine—in helical/hydrophobic microenvironments. In membrane proteins it emphasizes the aromatic belt at transmembrane helix boundaries and ligand/solute-binding cores; in soluble enzymes it marks buried aromatic cores or pockets (including nucleotide-binding sites). Overall this reflects an “aromatic/hydrophobic microenvironment” signal rather than a family-specific motif.	9.06	25
#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	8.84	4
#6819	Proline-anchored strand-loop boundaries	Proline-anchored loop/turn motifs at beta-strand termini and strand–loop–strand connectors (often in P/Ser/Thr/Gly-rich segments), marking boundaries between ordered beta structure and coil/disorder and recurring in beta-rich/repeat architectures (e.g., LRR, beta-propeller) as well as soluble beta-grasp–like folds	8.77	6
#13745	Hydrophobic secondary structure signal	Generic hydrophobic secondary-structure signal: activates on hydrophobic/aromatic side chains that form stable α-helices and β-strands—covering transmembrane helices, coiled-coils, and the hydrophobic cores of globular domains—while avoiding catalytic/metal-binding residues and disordered segments	8.77	16
#13818	N-terminal domain start signal	Start-of-domain signal: the feature detects the transition into the first ordered secondary-structure elements at the N-terminus of a conserved globular domain (often immediately after a signal/transit peptide, lipidation site, or disordered tail), with strongest matches for cyclophilin-type PPIase folds and weaker matches for many other domain starts.	8.37	50
#8805	Exposed loops/termini CBX-enriched	Microfeature firing on isolated, mostly solvent-exposed residues in coils, turns, and at the ends of secondary structures, often near domain boundaries or in terminal tails, and not tied to catalytic or cofactor-binding sites. Strongly enriched on Polycomb chromobox (CBX) family proteins, where it picks up a conserved C-terminal region and a position within the Chromo domain.	8.36	4
#16214	Nontransmembrane beta strands/turns	A general secondary-structure signal for short beta-strands and their flanking turns/coil in non-transmembrane regions (extracellular or cytosolic), with a preference for small/flexible or polar/charged residues; strongly depleted in alpha-helices, especially membrane-spanning helices.	8.36	3
#220	Phenylalanine-rich hydrophobic motif detector	Phenylalanine-focused residue identity feature: detects Phe (F) residues, with a preference for F-rich, hydrophobic stretches (e.g., signal peptides and transmembrane helices), but independent of secondary structure or specific function	8.30	6
#1911	Solvent-exposed beta-sheet edges	Solvent‑exposed residues in well‑ordered β‑strands and their adjoining turns, especially edge/terminal strands of β‑sheets in β‑sandwich or α/β enzyme cores (often in extracellular/periplasmic/ER‑lumenal domains and near β‑sheet→TM junctions), enriched for acidic/hydroxyl residues with frequent Gly/Pro and occasional aromatics.	8.01	4
#14744	Extracellular beta-strand hydrophobics	Hydrophobic residues positioned within well‑ordered β‑strands of β‑sheet architectures (e.g., β‑propellers, β‑sandwich/Ig‑like, and other β‑rich domains), especially in extracellular/periplasmic or lumenal portions of secreted and membrane‑associated proteins; the signal avoids helices, transmembrane segments, glycosylation/metal‑binding sites, and most disulfide‑anchored positions.	7.83	4
#10600	Hydrophobic beta-strand preference	Preference for hydrophobic residues (Leu/Val/Ile/Phe/Tyr/Met, also Ala) occupying beta‑strand positions in well‑ordered beta‑sheet regions across diverse proteins; a structural, not function‑specific, signal that favors aliphatic/aromatic and small hydrophobic side chains in beta‑strands while avoiding helices, transmembranes, signal peptides, and disordered segments.	7.61	5
#14447	Secondary structure capping residues	Residues that cap or initiate secondary‑structure elements—especially helix N‑caps/first helical turns and β‑strand termini/adjacent turns—across many folds; frequently realized in structured propeptides and extracellular/periplasmic domains, but not tied to catalytic sites.	7.53	5
#9291	Catalytic metal binding beta strands	Active-site beta-strand and adjacent residues that position acidic side chains for divalent metal (Mg2+/Zn2+) and phosphate/nucleotide interactions; the feature preferentially marks these catalytic-core motifs across phosphohydrolases and isomerases, and analogous segments adjacent to catalytic residues in other enzyme folds (e.g., UBC E2, YrdC-like, complex I assembly factors).	7.42	12
#8085	OB-fold AEWGEG turn	A short conserved motif centered on an aromatic-glycine turn, matching an A-E-W-G-(E/Y)-G consensus that caps a β-strand and initiates a β→coil/helix transition in the C-terminal OB-fold-like region of ATP-dependent DNA ligases. The motif lies distal to catalytic and ATP-binding residues.	7.38	7
#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.	7.21	2
#14895	Unknown generic feature	Unknown generic feature	23.75	80
#9214	Unknown generic feature	Unknown generic feature	18.33	80
#1803	Unknown generic feature	Unknown generic feature	15.97	79
#14534	Unknown generic feature	Unknown generic feature	15.57	78
#9194	Unknown generic feature	Unknown generic feature	15.21	80
#9005	Unknown generic feature	Unknown generic feature	11.52	67

Clinical variants

Differential region — lost N-terminus (canonical-only)

Pos (iso)	AA change	Consequence	Source	Clin. sig.	AF (gnomAD)	Impact	AlphaMissense	ESM-C ΔLLR	Link
—	M→K	intronic	gnomAD	—	7.81e-07	damaging	—	-11.25	chr19-531933-T-A
—	A→S	intronic	gnomAD	—	7.79e-07	—	likely_benign (0.08)	-6.68	chr19-531935-G-T
—	A→A	intronic	gnomAD	—	1.56e-06	—	—	0.00	chr19-531937-T-C
—	P→Q	intronic	gnomAD	—	7.74e-07	damaging	likely_benign (0.08)	-7.75	chr19-531942-C-A
—	P→R	intronic	gnomAD	—	7.74e-07	damaging	likely_benign (0.14)	-10.18	chr19-531942-C-G
—	P→P	intronic	gnomAD	—	4.65e-06	—	—	0.00	chr19-531943-G-A
—	L→I	intronic	gnomAD	—	3.84e-06	damaging	likely_benign (0.08)	-7.90	chr19-531944-C-A
—	L→V	intronic	gnomAD	—	7.67e-07	—	likely_benign (0.05)	-6.96	chr19-531944-C-G
—	V→M	intronic	gnomAD	—	1.15e-05	—	likely_benign (0.20)	-6.96	chr19-531947-G-A
—	V→A	intronic	gnomAD	—	7.66e-07	—	likely_benign (0.13)	-6.84	chr19-531948-T-C
—	V→V	intronic	gnomAD	—	4.57e-06	—	—	0.00	chr19-531949-G-T
—	P→R	intronic	gnomAD	—	7.61e-07	damaging	likely_benign (0.32)	-11.12	chr19-531951-C-G
—	P→L	intronic	gnomAD	—	7.61e-07	damaging	likely_benign (0.30)	-9.18	chr19-531951-C-T
—	P→P	intronic	gnomAD	—	7.61e-07	—	—	0.00	chr19-531952-C-G
—	Q→E	intronic	gnomAD	—	7.58e-07	damaging	likely_benign (0.16)	-10.37	chr19-531959-C-G
—	Q→Q	intronic	gnomAD	—	7.57e-07	—	—	0.00	chr19-531961-G-A
—	K→E	intronic	gnomAD	—	7.57e-07	damaging	likely_pathogenic (0.90)	-9.06	chr19-531962-A-G
—	K→N	intronic	gnomAD	—	4.54e-06	damaging	likely_pathogenic (0.95)	-8.49	chr19-531964-G-T
—	A→S	intronic	gnomAD	—	7.56e-07	damaging	ambiguous (0.50)	-9.37	chr19-531965-G-T
—	A→V	intronic	gnomAD	—	1.51e-06	damaging	likely_pathogenic (0.61)	-9.00	chr19-531966-C-T
—	A→A	intronic	gnomAD	—	3.03e-06	—	—	0.00	chr19-531967-G-A
—	L→L	intronic	gnomAD	—	7.53e-07	—	—	0.00	chr19-531973-G-A
—	L→L	intronic	gnomAD	—	1.13e-05	—	—	0.00	chr19-531973-G-T
—	L→L	intronic	gnomAD	—	3.77e-06	—	—	0.00	chr19-531974-C-T
—	L→R	intronic	gnomAD	—	7.53e-07	damaging	ambiguous (0.43)	-9.50	chr19-531975-T-G
—	L→V	intronic	gnomAD	—	7.50e-07	damaging	ambiguous (0.51)	-9.62	chr19-531980-C-G
—	L→F	intronic	gnomAD	—	1.50e-06	—	likely_benign (0.23)	-7.09	chr19-531980-C-T
—	L→P	intronic	gnomAD	—	1.50e-06	damaging	likely_pathogenic (1.00)	-11.06	chr19-531981-T-C
—	—	intronic	gnomAD	—	1.50e-06	damaging	—	—	chr19-531984-A-AG
—	K→K	intronic	gnomAD	—	2.24e-06	—	—	0.00	chr19-531985-G-A
—	—	intronic	gnomAD	—	2.99e-06	damaging	—	—	chr19-531986-G-GA
—	G→E	intronic	gnomAD	—	7.46e-07	damaging	ambiguous (0.51)	-9.18	chr19-531987-G-A
—	G→G	intronic	gnomAD	—	7.46e-07	—	—	0.00	chr19-531988-G-T
—	Q→L	intronic	gnomAD	—	7.44e-07	—	likely_benign (0.24)	-7.43	chr19-531993-A-T
—	E→K	intronic	gnomAD	—	7.43e-06	damaging	ambiguous (0.50)	-7.96	chr19-531995-G-A
—	E→K	intronic	gnomAD	—	5.94e-06	damaging	likely_pathogenic (0.71)	-10.44	chr19-531998-G-A
—	—	intronic	gnomAD	—	7.42e-07	damaging	—	—	chr19-531998-G-GAGCC
—	P→Q	intronic	gnomAD	—	7.41e-07	damaging	likely_pathogenic (0.84)	-10.44	chr19-532002-C-A
—	P→R	intronic	gnomAD	—	2.22e-06	damaging	likely_pathogenic (0.82)	-10.94	chr19-532002-C-G
—	P→L	intronic	gnomAD	—	7.41e-07	damaging	likely_pathogenic (0.89)	-9.31	chr19-532002-C-T
—	P→P	intronic	gnomAD	—	2.96e-06	—	—	0.00	chr19-532003-G-A
—	P→P	intronic	gnomAD	—	7.40e-07	—	—	0.00	chr19-532003-G-C
—	V→L	intronic	gnomAD	—	7.39e-07	damaging	likely_pathogenic (0.67)	-8.50	chr19-532004-G-C
—	V→V	intronic	gnomAD	—	7.39e-07	—	—	0.00	chr19-532006-C-T
—	E→E	intronic	gnomAD	—	1.47e-06	—	—	0.00	chr19-532009-G-A
—	E→D	intronic	gnomAD	—	2.21e-06	damaging	likely_pathogenic (0.96)	-8.81	chr19-532009-G-C
—	E→D	intronic	gnomAD	—	7.37e-07	damaging	likely_pathogenic (0.96)	-8.81	chr19-532009-G-T
—	G→G	intronic	gnomAD	—	2.21e-06	—	—	0.00	chr19-532012-A-C
—	F→F	intronic	gnomAD	—	2.21e-06	—	—	0.00	chr19-532015-C-T
—	R→L	intronic	gnomAD	—	7.35e-07	damaging	ambiguous (0.39)	-9.66	chr19-532017-G-T
—	R→R	intronic	gnomAD	—	1.47e-06	—	—	0.00	chr19-532018-C-T
—	—	intronic	gnomAD	—	7.34e-07	damaging	—	—	chr19-532018-CGT-C
—	T→I	intronic	gnomAD	—	7.33e-07	damaging	likely_benign (0.31)	-8.18	chr19-532023-C-T
—	T→T	intronic	gnomAD	—	7.33e-07	—	—	0.00	chr19-532024-A-G
—	L→L	intronic	gnomAD	—	7.32e-07	—	—	0.00	chr19-532025-C-T
—	V→M	intronic	gnomAD	—	7.32e-07	—	likely_benign (0.27)	-3.69	chr19-532028-G-A
—	V→L	intronic	gnomAD	—	7.32e-07	—	likely_benign (0.24)	-4.62	chr19-532028-G-C
—	V→V	intronic	gnomAD	—	1.46e-06	—	—	0.00	chr19-532030-G-A
—	D→N	intronic	gnomAD	—	7.32e-07	—	likely_benign (0.14)	-6.62	chr19-532031-G-A
—	D→G	intronic	gnomAD	—	7.32e-07	damaging	likely_benign (0.23)	-8.87	chr19-532032-A-G
—	D→E	intronic	gnomAD	—	1.46e-06	—	likely_benign (0.13)	-5.12	chr19-532033-C-G
—	E→K	intronic	gnomAD	—	1.17e-05	damaging	ambiguous (0.49)	-9.75	chr19-532034-G-A
—	E→E	intronic	gnomAD	—	4.67e-05	—	—	0.00	chr19-532036-G-A
—	E→D	intronic	gnomAD	—	7.30e-07	—	likely_benign (0.08)	-6.19	chr19-532036-G-C
—	E→D	intronic	gnomAD	—	2.19e-06	—	likely_benign (0.08)	-6.19	chr19-532036-G-T
—	G→S	intronic	gnomAD	—	3.65e-06	—	likely_benign (0.06)	-6.02	chr19-532037-G-A
—	G→V	intronic	gnomAD	—	7.31e-07	damaging	likely_benign (0.18)	-8.67	chr19-532038-G-T
—	G→G	intronic	gnomAD	—	7.31e-07	—	—	0.00	chr19-532039-C-A
—	G→G	intronic	gnomAD	—	7.31e-07	—	—	0.00	chr19-532039-C-G
—	G→G	intronic	gnomAD	—	1.46e-06	—	—	0.00	chr19-532039-C-T
—	D→N	intronic	gnomAD	—	7.31e-07	—	likely_benign (0.27)	-7.25	chr19-532040-G-A
—	D→E	intronic	gnomAD	—	7.31e-07	damaging	likely_pathogenic (0.71)	-10.37	chr19-532042-T-A
—	D→E	intronic	gnomAD	—	7.31e-07	damaging	likely_pathogenic (0.71)	-10.37	chr19-532042-T-G
—	L→Q	intronic	gnomAD	—	7.31e-07	damaging	likely_pathogenic (0.86)	-13.94	chr19-532044-T-A
—	L→R	intronic	gnomAD	—	3.65e-06	damaging	likely_pathogenic (0.89)	-12.69	chr19-532044-T-G
—	L→L	intronic	gnomAD	—	1.02e-05	—	—	0.00	chr19-532045-A-G
—	Y→C	intronic	gnomAD	—	1.46e-06	damaging	ambiguous (0.43)	-9.50	chr19-532047-A-G
—	Y→F	intronic	gnomAD	—	7.30e-07	damaging	likely_benign (0.15)	-9.19	chr19-532047-A-T
—	N→S	intronic	gnomAD	—	7.30e-07	—	likely_benign (0.07)	-6.31	chr19-532050-A-G
—	N→N	intronic	gnomAD	—	6.57e-06	—	—	0.00	chr19-532051-C-T
—	A→T	intronic	gnomAD	—	2.92e-06	damaging	likely_pathogenic (0.87)	-8.31	chr19-532061-G-A
—	A→S	intronic	gnomAD	—	7.30e-07	damaging	ambiguous (0.44)	-7.65	chr19-532061-G-T
—	A→V	intronic	gnomAD	—	2.19e-06	damaging	likely_pathogenic (0.84)	-8.50	chr19-532062-C-T
—	A→A	intronic	gnomAD	—	7.30e-07	—	—	0.00	chr19-532063-C-A
—	I→I	intronic	gnomAD	—	9.14e-02	—	—	0.00	chr19-532066-C-T
—	—	intronic	gnomAD	—	7.30e-07	damaging	—	—	chr19-532068-TC-T
—	G→V	intronic	gnomAD	—	7.30e-07	damaging	likely_pathogenic (1.00)	-13.12	chr19-532071-G-T
—	G→G	intronic	gnomAD	—	7.30e-07	—	—	0.00	chr19-532072-G-C
—	—	intronic	gnomAD	—	1.46e-06	damaging	—	—	chr19-532072-G-GC
—	—	intronic	gnomAD	—	2.19e-06	damaging	—	—	chr19-532072-GC-G
—	P→S	intronic	gnomAD	—	1.46e-06	damaging	likely_pathogenic (0.99)	-9.81	chr19-532073-C-T
—	P→H	intronic	gnomAD	—	7.30e-07	damaging	likely_pathogenic (1.00)	-12.87	chr19-532074-C-A
—	P→L	intronic	gnomAD	—	1.46e-06	damaging	likely_pathogenic (0.99)	-10.56	chr19-532074-C-T
—	P→P	intronic	gnomAD	—	1.46e-06	—	—	0.00	chr19-532075-C-T
—	P→S	intronic	gnomAD	—	2.92e-06	damaging	likely_pathogenic (0.99)	-8.18	chr19-532076-C-T
—	P→P	intronic	gnomAD	—	2.19e-06	—	—	0.00	chr19-532078-C-A
—	P→P	intronic	gnomAD	—	1.46e-06	—	—	0.00	chr19-532078-C-T
—	—	intronic	gnomAD	—	1.46e-06	damaging	—	—	chr19-532079-AAC-A
—	T→T	intronic	gnomAD	—	1.02e-05	—	—	0.00	chr19-532084-C-T
—	Y→Y	intronic	gnomAD	—	4.46e-05	—	—	0.00	chr19-532087-C-T
—	Y→Y	intronic	gnomAD	—	1.47e-06	—	—	0.00	chr19-532090-C-T
—	E→K	intronic	gnomAD	—	1.47e-06	damaging	likely_pathogenic (0.95)	-10.25	chr19-532091-G-A
—	G→D	intronic	gnomAD	—	1.47e-06	damaging	likely_pathogenic (0.98)	-10.19	chr19-532095-G-A
—	G→G	intronic	gnomAD	—	2.20e-06	—	—	0.00	chr19-532096-C-A
—	G→G	intronic	gnomAD	—	7.34e-07	—	—	0.00	chr19-532096-C-G
—	G→G	intronic	gnomAD	—	1.39e-05	—	—	0.00	chr19-532096-C-T
—	G→G	intronic	gnomAD	—	1.47e-06	—	—	0.00	chr19-532099-C-T
—	Y→Y	intronic	gnomAD	—	7.37e-07	—	—	0.00	chr19-532102-C-T
—	F→L	intronic	gnomAD	—	7.38e-07	damaging	likely_pathogenic (0.99)	-10.37	chr19-532105-C-A
—	F→L	intronic	gnomAD	—	7.38e-07	damaging	likely_pathogenic (0.99)	-10.37	chr19-532105-C-G
—	F→F	intronic	gnomAD	—	1.40e-05	—	—	0.00	chr19-532105-C-T
—	K→R	intronic	gnomAD	—	1.48e-06	—	likely_benign (0.19)	-6.12	chr19-532107-A-G
—	K→K	intronic	gnomAD	—	7.41e-07	—	—	0.00	chr19-532108-G-A
—	A→T	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.97)	-9.19	chr19-535837-G-A
—	A→V	intronic	gnomAD	—	2.05e-06	damaging	likely_pathogenic (0.98)	-10.25	chr19-535838-C-T
—	A→A	intronic	gnomAD	—	3.71e-04	—	—	0.00	chr19-535839-G-A
—	A→A	intronic	gnomAD	—	6.84e-07	—	—	0.00	chr19-535839-G-C
—	R→C	intronic	gnomAD	—	2.05e-05	—	likely_benign (0.16)	-6.81	chr19-535840-C-T
—	R→H	intronic	gnomAD	—	7.53e-06	—	likely_benign (0.09)	-5.65	chr19-535841-G-A
—	R→R	intronic	gnomAD	—	1.37e-06	—	—	0.00	chr19-535842-C-T
—	L→L	intronic	gnomAD	—	6.84e-07	—	—	0.00	chr19-535845-C-T
—	K→T	intronic	gnomAD	—	5.47e-06	damaging	likely_benign (0.25)	-8.10	chr19-535847-A-C
—	K→R	intronic	gnomAD	—	6.84e-07	—	likely_benign (0.08)	-3.63	chr19-535847-A-G
—	K→K	intronic	gnomAD	—	1.37e-06	—	—	0.00	chr19-535848-G-A
—	P→P	intronic	gnomAD	—	1.37e-06	—	—	0.00	chr19-535854-C-T
—	I→V	intronic	gnomAD	—	1.57e-05	—	likely_benign (0.05)	-6.06	chr19-535855-A-G
—	I→F	intronic	gnomAD	—	6.84e-07	damaging	likely_benign (0.17)	-9.68	chr19-535855-A-T
—	I→T	intronic	gnomAD	—	6.84e-07	—	likely_benign (0.10)	-7.40	chr19-535856-T-C
—	I→I	intronic	gnomAD	—	1.37e-06	—	—	0.00	chr19-535857-C-A
—	I→M	intronic	gnomAD	—	6.84e-07	damaging	likely_benign (0.07)	-7.56	chr19-535857-C-G
—	I→I	intronic	gnomAD	—	9.58e-06	—	—	0.00	chr19-535857-C-T
—	D→N	intronic	gnomAD	—	2.05e-06	damaging	likely_pathogenic (0.66)	-8.06	chr19-535858-G-A
—	Y→N	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-13.62	chr19-535861-T-A
—	Y→C	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-11.81	chr19-535862-A-G
—	Y→Y	intronic	gnomAD	—	4.11e-06	—	—	0.00	chr19-535863-C-T
—	P→L	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-11.12	chr19-535865-C-T
—	P→P	intronic	gnomAD	—	1.37e-06	—	—	0.00	chr19-535866-A-G
—	Y→Y	intronic	gnomAD	—	6.16e-06	—	—	0.00	chr19-535869-C-T
—	P→T	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-11.81	chr19-535873-C-A
—	—	intronic	gnomAD	—	1.37e-06	damaging	—	—	chr19-535873-CCA-C
—	P→L	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-10.31	chr19-535874-C-T
—	P→S	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-10.81	chr19-535876-C-T
—	P→P	intronic	gnomAD	—	6.84e-06	—	—	0.00	chr19-535878-A-G
—	A→G	intronic	gnomAD	—	6.84e-07	damaging	likely_benign (0.23)	-9.00	chr19-535880-C-G
—	A→V	intronic	gnomAD	—	3.42e-06	—	likely_benign (0.19)	-7.28	chr19-535880-C-T
—	A→A	intronic	gnomAD	—	6.84e-07	—	—	0.00	chr19-535881-C-A
—	A→A	intronic	gnomAD	—	6.84e-07	—	—	0.00	chr19-535881-C-T
—	—	intronic	gnomAD	—	6.84e-07	damaging	—	—	chr19-535881-CT-C
—	F→L	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.97)	-8.50	chr19-535882-T-C
—	R→W	intronic	gnomAD	—	4.11e-06	damaging	likely_pathogenic (0.74)	-10.69	chr19-535885-C-T
—	R→Q	intronic	gnomAD	—	4.86e-05	damaging	likely_benign (0.21)	-8.25	chr19-535886-G-A
—	R→R	intronic	gnomAD	—	2.05e-06	—	—	0.00	chr19-535887-G-T
—	F→F	intronic	gnomAD	—	1.51e-05	—	—	0.00	chr19-535890-C-T
—	L→L	intronic	gnomAD	—	8.89e-06	—	—	0.00	chr19-535891-C-T
—	L→L	intronic	gnomAD	—	2.06e-04	—	—	0.00	chr19-535893-G-A
—	T→A	intronic	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.70)	-11.00	chr19-535894-A-G
—	A→V	intronic	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (0.84)	-8.50	ClinVar:2273958
—	A→S	intronic	ClinVar	Uncertain significance	—	—	likely_benign (0.08)	-6.68	ClinVar:3264959
—	R→Q	intronic	ClinVar	Uncertain significance	—	—	likely_benign (0.16)	-4.32	ClinVar:3264960
—	R→Q	intronic	ClinVar	Uncertain significance	—	damaging	likely_benign (0.21)	-8.25	ClinVar:3998494
—	R→C	intronic	ClinVar	Uncertain significance	—	—	likely_benign (0.16)	-6.81	ClinVar:4223244
—	E→K	intronic	ClinVar	Uncertain significance	—	damaging	ambiguous (0.50)	-7.96	ClinVar:4223245
—	R→R	intronic	ClinVar	—	—	—	—	0.00	ClinVar:4444417
—	R→L	intronic	ClinVar	—	—	damaging	likely_pathogenic (0.80)	-10.94	ClinVar:4444418
—	V→A	intronic	ClinVar	Uncertain significance	—	—	likely_benign (0.13)	-6.84	ClinVar:4650835
—	Y→H	intronic	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (1.00)	-12.31	ClinVar:4650836
—	V→A	intronic	COSMIC	—	—	—	likely_benign (0.13)	-6.84	COSV53118206
—	V→V	intronic	COSMIC	—	—	—	—	0.00	COSV53117784
—	Q→H	intronic	COSMIC	—	—	—	ambiguous (0.56)	-7.50	COSV53117487
—	D→N	intronic	COSMIC	—	—	—	likely_benign (0.14)	-6.62	COSV53116218
—	E→K	intronic	COSMIC	—	—	damaging	ambiguous (0.49)	-9.75	COSV99296470
—	D→Y	intronic	COSMIC	—	—	damaging	likely_pathogenic (0.87)	-12.69	COSV99296439
—	W→*	intronic	COSMIC	—	—	damaging	—	—	COSV53117251
—	V→V	intronic	COSMIC	—	—	—	—	0.00	COSV53115899
—	A→V	intronic	COSMIC	—	—	damaging	likely_pathogenic (0.84)	-8.50	COSV105074737
—	I→I	intronic	COSMIC	—	—	—	—	0.00	COSV53117836
—	F→F	intronic	COSMIC	—	—	—	—	0.00	COSV104571653
—	P→L	intronic	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-9.18	COSV53115992
—	P→P	intronic	COSMIC	—	—	—	—	0.00	COSV99296214
—	G→G	intronic	COSMIC	—	—	—	—	0.00	COSV53118380
—	A→V	intronic	COSMIC	—	—	damaging	likely_pathogenic (0.98)	-10.25	COSV53116787
—	R→C	intronic	COSMIC	—	—	—	likely_benign (0.16)	-6.81	COSV53116161
—	P→S	intronic	COSMIC	—	—	damaging	likely_pathogenic (0.97)	-9.37	COSV53118129
—	P→P	intronic	COSMIC	—	—	—	—	0.00	COSV53117104
—	I→I	intronic	COSMIC	—	—	—	—	0.00	COSV53117230
—	D→V	intronic	COSMIC	—	—	damaging	likely_pathogenic (0.98)	-12.12	COSV105074698
—	P→R	intronic	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-12.37	COSV104571676
—	A→T	intronic	COSMIC	—	—	—	likely_benign (0.08)	-6.12	COSV53117194
—	R→W	intronic	COSMIC	—	—	damaging	likely_pathogenic (0.74)	-10.69	COSV53118423
—	R→Q	intronic	COSMIC	—	—	damaging	likely_benign (0.21)	-8.25	COSV53117018
—	F→F	intronic	COSMIC	—	—	—	—	0.00	COSV53116027

191 variants in the differential region.

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

Pos (iso)	AA change	Consequence	Source	Clin. sig.	AF (gnomAD)	Impact	AlphaMissense	ESM-C ΔLLR	Link
0	K→K	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-535899-G-A
1	M→L	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.68)	-7.31	chr19-535900-A-T
1	M→I	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.92)	-8.19	COSV108753965
2	W→*	stop_gained	gnomAD	—	6.84e-07	LoF	—	—	chr19-535904-G-A
2	W→*	stop_gained	gnomAD	—	6.84e-07	LoF	—	—	chr19-535905-G-A
3	H→R	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (1.00)	-11.81	chr19-535907-A-G
3	H→H	synonymous_variant	gnomAD	—	8.21e-06	—	—	0.00	chr19-535908-C-T
4	P→S	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-12.12	chr19-535909-C-T
4	P→R	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-14.12	chr19-535910-C-G
4	P→P	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-535911-T-C
5	N→K	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-11.62	chr19-535914-C-A
5	N→N	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-535914-C-T
6	I→I	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-535917-C-A
6	I→M	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-11.50	chr19-535917-C-G
7	Y→*	stop_gained	gnomAD	—	6.85e-07	LoF	—	—	chr19-535920-C-G
7	Y→Y	synonymous_variant	gnomAD	—	8.22e-06	—	—	0.00	chr19-535920-C-T
7	Y→C	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.97)	-11.50	COSV99296436
8	E→K	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (0.91)	-10.62	chr19-535921-G-A
8	—	frameshift_variant	gnomAD	—	6.84e-07	LoF	—	—	chr19-535921-GA-G
8	E→E	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-535923-G-A
8	E→K	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (0.91)	-10.62	ClinVar:4223247
9	T→K	missense_variant	gnomAD	—	6.89e-07	damaging	likely_pathogenic (0.81)	-10.05	chr19-536244-C-A
9	T→M	missense_variant	gnomAD	—	2.76e-06	damaging	ambiguous (0.45)	-7.68	chr19-536244-C-T
9	—	inframe_deletion	gnomAD	—	6.89e-07	—	—	—	chr19-536244-CGGG-C
9	T→T	synonymous_variant	gnomAD	—	1.46e-03	—	—	0.00	chr19-536245-G-A
9	T→T	synonymous_variant	gnomAD	—	2.07e-06	—	—	0.00	chr19-536245-G-C
9	T→T	synonymous_variant	gnomAD	—	1.24e-05	—	—	0.00	chr19-536245-G-T
9	T→T	synonymous_variant	ClinVar	—	—	—	—	0.00	ClinVar:4444433
10	G→G	synonymous_variant	gnomAD	—	4.13e-06	—	—	0.00	chr19-536248-G-A
10	G→G	synonymous_variant	gnomAD	—	6.88e-07	—	—	0.00	chr19-536248-G-T
10	G→E	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (1.00)	-12.81	ClinVar:4223246
10	G→E	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-12.81	COSV99296367
11	D→H	missense_variant	gnomAD	—	6.88e-07	damaging	likely_pathogenic (0.94)	-10.81	chr19-536249-G-C
11	D→G	missense_variant	gnomAD	—	6.88e-07	damaging	likely_pathogenic (0.95)	-9.93	chr19-536250-A-G
11	D→E	missense_variant	gnomAD	—	6.88e-07	—	ambiguous (0.53)	-5.06	chr19-536251-C-A
11	D→D	synonymous_variant	gnomAD	—	3.37e-05	—	—	0.00	chr19-536251-C-T
11	D→A	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.86)	-10.06	COSV99296304
11	D→D	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53116733
12	V→M	missense_variant	gnomAD	—	1.38e-06	damaging	likely_pathogenic (0.99)	-13.25	chr19-536252-G-A
12	V→L	missense_variant	gnomAD	—	6.88e-07	damaging	likely_pathogenic (0.93)	-11.00	chr19-536252-G-T
12	V→A	missense_variant	gnomAD	—	1.38e-06	damaging	likely_pathogenic (0.99)	-12.00	chr19-536253-T-C
12	V→V	synonymous_variant	gnomAD	—	6.88e-07	—	—	0.00	chr19-536254-G-A
13	C→S	missense_variant	gnomAD	—	6.88e-07	damaging	likely_pathogenic (1.00)	-12.06	chr19-536256-G-C
14	I→I	synonymous_variant	gnomAD	—	6.19e-06	—	—	0.00	chr19-536260-C-A
14	I→I	synonymous_variant	gnomAD	—	1.31e-05	—	—	0.00	chr19-536260-C-T
15	S→S	synonymous_variant	gnomAD	—	6.88e-06	—	—	0.00	chr19-536263-C-T
16	I→I	synonymous_variant	gnomAD	—	3.92e-05	—	—	0.00	chr19-536266-C-T
16	I→I	synonymous_variant	ClinVar	Likely benign	—	—	—	0.00	ClinVar:3488348
16	I→T	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-10.75	COSV53116052
17	L→F	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (1.00)	-12.37	chr19-536267-C-T
17	L→P	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-12.31	COSV53116063
18	H→Q	missense_variant	gnomAD	—	6.86e-07	damaging	likely_pathogenic (1.00)	-12.12	chr19-536272-C-G
18	H→P	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.81	COSV53115911
19	P→L	missense_variant	gnomAD	—	2.06e-06	damaging	likely_pathogenic (0.83)	-9.50	chr19-536274-C-T
19	P→P	synonymous_variant	gnomAD	—	2.74e-05	—	—	0.00	chr19-536275-G-A
19	P→S	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.62)	-8.06	COSV104571657
20	P→L	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.99)	-10.94	chr19-536277-C-T
20	P→P	synonymous_variant	gnomAD	—	6.51e-05	—	—	0.00	chr19-536278-G-A
20	P→P	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-536278-G-T
20	P→Q	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-12.87	COSV99296263
21	V→M	missense_variant	gnomAD	—	9.59e-05	damaging	ambiguous (0.35)	-8.81	chr19-536279-G-A
21	V→E	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.84)	-13.31	chr19-536280-T-A
21	V→A	missense_variant	gnomAD	—	6.85e-07	damaging	ambiguous (0.55)	-8.81	chr19-536280-T-C
21	V→M	missense_variant	ClinVar	Uncertain significance	—	damaging	ambiguous (0.35)	-8.81	ClinVar:2323973
22	D→Y	missense_variant	gnomAD	—	2.74e-06	damaging	likely_pathogenic (0.93)	-11.81	chr19-536282-G-T
22	D→G	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.88)	-11.62	chr19-536283-A-G
22	D→E	missense_variant	gnomAD	—	4.11e-06	damaging	likely_pathogenic (0.67)	-8.06	chr19-536284-C-G
22	D→D	synonymous_variant	gnomAD	—	4.79e-06	—	—	0.00	chr19-536284-C-T
22	D→D	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99296220
23	D→N	missense_variant	gnomAD	—	2.05e-06	damaging	likely_pathogenic (0.97)	-9.62	chr19-536285-G-A
23	D→E	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (1.00)	-11.12	chr19-536287-C-A
23	D→D	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-536287-C-T
24	P→H	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.85)	-13.81	chr19-536289-C-A
24	P→P	synonymous_variant	gnomAD	—	4.79e-06	—	—	0.00	chr19-536290-C-G
26	S→G	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.80)	-13.06	chr19-536294-A-G
26	S→S	synonymous_variant	gnomAD	—	4.11e-05	—	—	0.00	chr19-536296-C-T
26	—	frameshift_variant	gnomAD	—	6.85e-07	LoF	—	—	chr19-536296-CG-C
27	G→R	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (1.00)	-10.75	chr19-536297-G-A
27	G→R	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (1.00)	-10.75	chr19-536297-G-C
27	G→E	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (1.00)	-11.81	chr19-536298-G-A
27	G→A	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.98)	-11.94	chr19-536298-G-C
27	G→V	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (0.99)	-13.31	chr19-536298-G-T
27	G→G	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-536299-G-A
27	G→R	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (1.00)	-10.75	ClinVar:3829750
27	G→R	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-10.75	COSV99296200
27	G→W	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-14.75	COSV99296211
27	G→E	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.81	COSV53116970
28	E→K	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (1.00)	-12.75	chr19-536300-G-A
28	E→*	stop_gained	gnomAD	—	6.85e-07	LoF	—	—	chr19-536300-G-T
28	E→E	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-536302-G-A
29	L→L	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-536305-G-A
30	P→L	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.92)	-9.81	chr19-536307-C-T
30	P→P	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-536308-C-T
31	S→S	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-536311-A-T
31	S→S	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53116775
33	R→G	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (1.00)	-13.50	chr19-536315-A-G
33	R→K	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.97)	-12.75	chr19-536316-G-A
34	W→S	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (1.00)	-15.50	chr19-536319-G-C
34	W→G	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-13.06	COSV105074728
34	W→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-14.81	COSV53118165
35	—	mnv	COSMIC	—	—	—	—	—	COSV53118327
35	N→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.81	COSV99296456
36	P→L	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (1.00)	-12.75	chr19-536325-C-T
36	P→S	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-12.06	COSV53117330
36	P→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-12.75	COSV99296458
37	T→T	synonymous_variant	gnomAD	—	6.85e-06	—	—	0.00	chr19-536329-G-A
37	T→T	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-536329-G-T
37	T→T	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53116865
38	Q→Q	synonymous_variant	gnomAD	—	6.85e-06	—	—	0.00	chr19-536332-G-A
39	N→H	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.71)	-13.31	chr19-536333-A-C
39	N→S	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.16)	-8.25	chr19-536334-A-G
39	N→K	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.98)	-12.19	chr19-536335-C-G
39	N→N	synonymous_variant	gnomAD	—	1.72e-04	—	—	0.00	chr19-536335-C-T
40	—	frameshift_variant	gnomAD	—	2.06e-06	LoF	—	—	chr19-536336-GTCAGGTAAGCCGGCCCAACCCCCTGTGTCCACCCAGAACA-G
42	T→I	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-13.12	chr19-537015-C-T
42	T→A	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.97)	-12.06	COSV99296450
42	T→I	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-13.12	COSV53116744
44	L→F	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.97)	-11.87	chr19-537020-C-T
44	L→L	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537022-C-T
45	L→L	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-537023-C-T
46	S→C	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-13.50	chr19-537026-A-T
46	S→S	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537028-T-C
47	V→V	synonymous_variant	gnomAD	—	1.30e-05	—	—	0.00	chr19-537031-G-A
48	I→L	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.74)	-9.81	chr19-537032-A-C
48	I→V	missense_variant	gnomAD	—	6.84e-07	damaging	ambiguous (0.43)	-7.94	chr19-537032-A-G
48	I→I	synonymous_variant	gnomAD	—	4.30e-04	—	—	0.00	chr19-537034-C-A
48	I→M	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.91)	-10.56	chr19-537034-C-G
48	I→I	synonymous_variant	gnomAD	—	4.79e-06	—	—	0.00	chr19-537034-C-T
49	S→C	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.96)	-10.94	chr19-537036-C-G
49	S→F	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-12.44	chr19-537036-C-T
49	S→S	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537037-C-G
49	S→S	synonymous_variant	gnomAD	—	8.21e-06	—	—	0.00	chr19-537037-C-T
49	—	mnv	COSMIC	—	—	—	—	—	COSV53118226
50	L→F	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-11.44	chr19-537038-C-T
50	L→L	synonymous_variant	gnomAD	—	8.21e-06	—	—	0.00	chr19-537040-C-G
51	L→L	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-537043-G-A
52	N→N	synonymous_variant	gnomAD	—	1.18e-03	—	—	0.00	chr19-537046-C-T
52	N→N	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99296495
53	E→K	missense_variant	gnomAD	—	2.05e-06	damaging	likely_pathogenic (1.00)	-11.00	chr19-537047-G-A
53	E→K	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-11.00	COSV53117687
54	P→A	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-12.31	chr19-537050-C-G
54	P→L	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-12.37	chr19-537051-C-T
54	P→P	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-537052-C-T
56	T→I	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (0.57)	-11.25	chr19-537057-C-T
56	—	inframe_deletion	gnomAD	—	6.84e-07	—	—	—	chr19-537057-CCTT-C
56	T→T	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537058-C-T
57	F→I	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.87)	-12.75	chr19-537059-T-A
57	F→Y	missense_variant	gnomAD	—	6.84e-07	damaging	likely_benign (0.13)	-8.31	chr19-537060-T-A
57	F→S	missense_variant	gnomAD	—	1.37e-06	damaging	likely_benign (0.30)	-8.50	chr19-537060-T-C
57	—	inframe_deletion	COSMIC	—	—	—	—	—	COSV99296351
58	S→L	missense_variant	gnomAD	—	2.74e-06	damaging	likely_pathogenic (1.00)	-12.12	chr19-537063-C-T
58	S→S	synonymous_variant	gnomAD	—	1.51e-05	—	—	0.00	chr19-537064-G-A
58	S→S	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537064-G-T
58	S→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-12.12	COSV104571668
59	P→P	synonymous_variant	gnomAD	—	1.03e-05	—	—	0.00	chr19-537067-C-T
59	P→P	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53118273
60	A→T	missense_variant	gnomAD	—	3.42e-06	damaging	likely_pathogenic (1.00)	-10.50	chr19-537068-G-A
60	A→T	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-10.50	COSV53118485
61	N→N	synonymous_variant	gnomAD	—	1.23e-05	—	—	0.00	chr19-537073-C-T
61	N→N	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53116576
62	V→M	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-10.25	chr19-537074-G-A
63	D→D	synonymous_variant	gnomAD	—	1.03e-05	—	—	0.00	chr19-537079-C-T
64	A→T	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (1.00)	-12.00	chr19-537080-G-A
64	A→D	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-13.87	chr19-537081-C-A
64	A→A	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-537082-C-T
65	S→S	synonymous_variant	gnomAD	—	4.11e-06	—	—	0.00	chr19-537085-C-A
65	S→S	synonymous_variant	gnomAD	—	8.90e-06	—	—	0.00	chr19-537085-C-T
65	S→F	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (1.00)	-13.56	COSV53116039
65	S→S	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53118387
66	V→M	missense_variant	gnomAD	—	2.05e-06	damaging	likely_pathogenic (0.95)	-10.12	chr19-537086-G-A
66	V→V	synonymous_variant	gnomAD	—	9.58e-06	—	—	0.00	chr19-537088-G-A
66	V→M	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.95)	-10.12	COSV53116615
66	V→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.94)	-10.00	COSV53116797
67	M→R	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.97)	-10.87	chr19-537090-T-G
67	M→I	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.99)	-9.94	chr19-537091-G-A
68	Y→Y	synonymous_variant	gnomAD	—	6.16e-06	—	—	0.00	chr19-537094-C-T
69	R→R	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-537097-G-A
69	R→S	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (1.00)	-13.25	chr19-537097-G-T
69	R→R	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV53117206
70	K→R	missense_variant	gnomAD	—	2.74e-06	—	likely_benign (0.10)	-3.81	chr19-537099-A-G
70	K→K	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537100-G-A
70	K→R	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.10)	-3.81	ClinVar:3140825
71	W→L	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.99)	-12.56	COSV99296236
72	K→K	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537106-A-G
73	E→E	synonymous_variant	gnomAD	—	2.81e-05	—	—	0.00	chr19-537109-G-A
73	E→D	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.09)	-6.37	chr19-537109-G-C
73	E→Q	missense_variant	COSMIC	—	—	damaging	ambiguous (0.55)	-14.37	COSV106337788
74	S→N	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.69)	-5.43	chr19-537111-G-A
74	S→S	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-537112-C-T
74	S→N	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.69)	-5.43	COSV53117872
74	S→I	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.94)	-12.43	COSV107230699
75	K→N	missense_variant	COSMIC	—	—	damaging	ambiguous (0.39)	-8.37	COSV108029097
76	G→G	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-537118-G-A
77	K→E	missense_variant	gnomAD	—	4.11e-06	damaging	likely_benign (0.23)	-7.52	chr19-537119-A-G
77	K→N	missense_variant	gnomAD	—	6.84e-07	damaging	ambiguous (0.54)	-7.70	chr19-537121-G-T
77	K→E	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_benign (0.23)	-7.52	ClinVar:3829751
78	D→N	missense_variant	gnomAD	—	6.84e-07	—	ambiguous (0.50)	-7.22	chr19-537122-G-A
78	D→Y	missense_variant	gnomAD	—	2.05e-06	damaging	likely_pathogenic (0.75)	-11.87	chr19-537122-G-T
78	D→D	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537124-T-C
79	R→W	missense_variant	gnomAD	—	1.37e-06	damaging	likely_benign (0.25)	-9.17	chr19-537125-C-T
79	R→Q	missense_variant	gnomAD	—	3.49e-05	—	likely_benign (0.08)	-6.64	chr19-537126-G-A
79	R→L	missense_variant	gnomAD	—	2.05e-06	damaging	likely_benign (0.26)	-9.23	chr19-537126-G-T
79	R→R	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-537127-G-A
79	R→Q	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.08)	-6.64	ClinVar:2368086
79	R→L	missense_variant	COSMIC	—	—	damaging	likely_benign (0.26)	-9.23	COSV108029108
80	E→K	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.80)	-11.56	chr19-537128-G-A
80	E→G	missense_variant	gnomAD	—	3.42e-06	damaging	likely_pathogenic (0.69)	-10.06	chr19-537129-A-G
80	E→E	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-537130-G-A
80	E→D	missense_variant	gnomAD	—	1.37e-06	—	ambiguous (0.35)	-7.31	chr19-537130-G-T
81	Y→Y	synonymous_variant	gnomAD	—	6.84e-07	—	—	0.00	chr19-537133-C-T
82	T→I	missense_variant	gnomAD	—	2.26e-05	—	likely_benign (0.16)	-1.87	chr19-537135-C-T
82	T→T	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-537136-A-G
83	—	inframe_deletion	gnomAD	—	1.37e-06	—	—	—	chr19-537138-ACAT-A
84	I→F	missense_variant	gnomAD	—	6.84e-07	damaging	likely_pathogenic (0.66)	-9.99	chr19-537140-A-T
84	I→I	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-537142-C-A
85	I→T	missense_variant	gnomAD	—	2.05e-06	damaging	likely_pathogenic (0.98)	-8.81	chr19-537144-T-C
85	I→I	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-537145-C-A
85	I→I	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-537145-C-T
86	—	frameshift_variant	gnomAD	—	6.85e-07	LoF	—	—	chr19-537146-C-CGGTGAGGGCG
86	R→W	missense_variant	gnomAD	—	6.85e-06	damaging	ambiguous (0.46)	-8.68	chr19-537146-C-T
86	R→Q	missense_variant	gnomAD	—	4.79e-06	—	likely_benign (0.14)	-6.84	chr19-537147-G-A
86	R→R	synonymous_variant	gnomAD	—	7.08e-07	—	—	0.00	chr19-541339-G-C
87	K→E	missense_variant	gnomAD	—	7.07e-07	damaging	likely_pathogenic (0.61)	-8.62	chr19-541340-A-G
87	K→M	missense_variant	gnomAD	—	7.06e-06	damaging	likely_pathogenic (0.71)	-9.81	chr19-541341-A-T
87	K→K	synonymous_variant	gnomAD	—	2.82e-06	—	—	0.00	chr19-541342-G-A
88	Q→E	missense_variant	COSMIC	—	—	damaging	ambiguous (0.54)	-11.25	COSV52742678
89	V→V	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99198812
90	L→P	missense_variant	gnomAD	—	1.40e-06	damaging	likely_pathogenic (0.91)	-9.87	chr19-541350-T-C
90	—	frameshift_variant	gnomAD	—	6.99e-07	LoF	—	—	chr19-541350-TG-T
91	G→G	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52742198
91	G→G	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52742721
93	K→M	missense_variant	gnomAD	—	1.39e-06	damaging	likely_benign (0.24)	-9.56	chr19-541359-A-T
93	K→K	synonymous_variant	gnomAD	—	8.32e-06	—	—	0.00	chr19-541360-G-A
94	V→A	missense_variant	gnomAD	—	6.93e-07	—	likely_benign (0.06)	-3.27	chr19-541362-T-C
94	V→V	synonymous_variant	gnomAD	—	6.92e-07	—	—	0.00	chr19-541363-G-A
95	D→Y	missense_variant	gnomAD	—	6.92e-07	damaging	likely_pathogenic (0.62)	-11.62	chr19-541364-G-T
95	D→G	missense_variant	gnomAD	—	6.92e-07	damaging	likely_pathogenic (0.69)	-10.50	chr19-541365-A-G
95	D→D	synonymous_variant	gnomAD	—	3.46e-05	—	—	0.00	chr19-541366-C-T
96	A→T	missense_variant	gnomAD	—	2.76e-06	damaging	likely_pathogenic (0.98)	-9.37	chr19-541367-G-A
96	A→E	missense_variant	gnomAD	—	6.90e-07	damaging	likely_pathogenic (1.00)	-13.37	chr19-541368-C-A
96	A→V	missense_variant	gnomAD	—	6.90e-07	damaging	likely_pathogenic (0.98)	-10.00	chr19-541368-C-T
96	A→A	synonymous_variant	gnomAD	—	7.58e-06	—	—	0.00	chr19-541369-G-A
96	A→V	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (0.98)	-10.00	ClinVar:2270762
96	A→T	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.98)	-9.37	COSV52742744
96	A→V	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.98)	-10.00	COSV52742969
96	A→A	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52742077
97	E→E	synonymous_variant	gnomAD	—	6.89e-07	—	—	0.00	chr19-541372-G-A
97	E→D	missense_variant	gnomAD	—	6.89e-07	—	likely_benign (0.15)	-4.61	chr19-541372-G-C
97	E→K	missense_variant	COSMIC	—	—	damaging	likely_benign (0.23)	-10.36	COSV99198838
98	R→C	missense_variant	gnomAD	—	2.75e-06	damaging	likely_benign (0.25)	-9.80	chr19-541373-C-T
98	R→H	missense_variant	gnomAD	—	4.82e-06	damaging	likely_benign (0.14)	-8.12	chr19-541374-G-A
98	R→P	missense_variant	gnomAD	—	6.88e-07	damaging	likely_pathogenic (0.97)	-12.93	chr19-541374-G-C
98	R→R	synonymous_variant	gnomAD	—	6.88e-07	—	—	0.00	chr19-541375-T-G
98	R→C	missense_variant	COSMIC	—	—	damaging	likely_benign (0.25)	-9.80	COSV52742398
98	R→R	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99198854
99	D→N	missense_variant	gnomAD	—	1.38e-06	damaging	likely_pathogenic (0.87)	-10.31	chr19-541376-G-A
99	D→D	synonymous_variant	gnomAD	—	1.51e-05	—	—	0.00	chr19-541378-C-T
100	G→S	missense_variant	gnomAD	—	1.37e-06	damaging	likely_benign (0.24)	-8.56	chr19-541379-G-A
100	G→C	missense_variant	gnomAD	—	6.87e-07	damaging	ambiguous (0.54)	-10.25	chr19-541379-G-T
100	G→G	synonymous_variant	gnomAD	—	6.87e-07	—	—	0.00	chr19-541381-C-T
101	V→M	missense_variant	gnomAD	—	8.92e-06	damaging	likely_pathogenic (0.68)	-7.56	chr19-541382-G-A
101	V→L	missense_variant	gnomAD	—	6.86e-07	damaging	likely_pathogenic (0.77)	-8.50	chr19-541382-G-T
101	V→V	synonymous_variant	gnomAD	—	6.86e-07	—	—	0.00	chr19-541384-G-A
102	K→Q	missense_variant	gnomAD	—	6.86e-07	damaging	likely_benign (0.11)	-8.24	chr19-541385-A-C
102	K→*	stop_gained	gnomAD	—	6.86e-07	LoF	—	—	chr19-541385-A-T
102	K→R	missense_variant	gnomAD	—	6.87e-07	—	likely_benign (0.08)	-5.37	chr19-541386-A-G
103	V→L	missense_variant	gnomAD	—	1.37e-06	damaging	likely_pathogenic (0.95)	-10.37	chr19-541388-G-T
103	V→V	synonymous_variant	gnomAD	—	4.18e-05	—	—	0.00	chr19-541390-G-A
103	V→V	synonymous_variant	gnomAD	—	2.74e-06	—	—	0.00	chr19-541390-G-C
104	P→A	missense_variant	gnomAD	—	6.86e-07	damaging	likely_pathogenic (0.98)	-12.62	chr19-541391-C-G
104	P→S	missense_variant	gnomAD	—	6.86e-07	damaging	likely_pathogenic (1.00)	-11.62	chr19-541391-C-T
104	P→P	synonymous_variant	gnomAD	—	6.86e-07	—	—	0.00	chr19-541393-C-T
105	T→T	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-541396-C-T
106	T→M	missense_variant	gnomAD	—	2.06e-06	damaging	likely_pathogenic (0.64)	-8.68	chr19-541398-C-T
106	T→T	synonymous_variant	gnomAD	—	1.58e-05	—	—	0.00	chr19-541399-G-A
106	T→A	missense_variant	COSMIC	—	—	damaging	ambiguous (0.48)	-8.99	COSV52741725
106	T→M	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.64)	-8.68	COSV52742017
107	L→V	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.13)	-9.25	chr19-541400-C-G
107	L→L	synonymous_variant	gnomAD	—	2.06e-06	—	—	0.00	chr19-541402-G-A
107	L→L	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-541402-G-C
108	A→T	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.12)	-5.60	chr19-541403-G-A
108	A→A	synonymous_variant	gnomAD	—	7.81e-05	—	—	0.00	chr19-541405-C-G
108	A→A	synonymous_variant	gnomAD	—	1.51e-05	—	—	0.00	chr19-541405-C-T
109	E→K	missense_variant	gnomAD	—	9.59e-06	damaging	likely_pathogenic (0.92)	-10.62	chr19-541406-G-A
109	E→*	stop_gained	gnomAD	—	6.85e-07	LoF	—	—	chr19-541406-G-T
109	E→A	missense_variant	gnomAD	—	6.85e-07	damaging	likely_pathogenic (0.64)	-9.18	chr19-541407-A-C
109	E→E	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-541408-G-A
109	E→D	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.24)	-5.68	chr19-541408-G-C
109	E→K	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (0.92)	-10.62	ClinVar:2615017
109	E→D	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.24)	-5.68	ClinVar:3998497
110	Y→Y	synonymous_variant	gnomAD	—	7.53e-06	—	—	0.00	chr19-541411-C-T
111	C→R	missense_variant	gnomAD	—	2.74e-06	damaging	likely_pathogenic (0.97)	-10.69	chr19-541412-T-C
111	C→C	synonymous_variant	gnomAD	—	2.05e-05	—	—	0.00	chr19-541414-C-T
111	C→Y	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (0.98)	-10.81	ClinVar:3488346
111	C→Y	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.98)	-10.81	COSV52742495
112	V→M	missense_variant	gnomAD	—	7.53e-06	damaging	likely_benign (0.23)	-8.05	chr19-541415-G-A
112	V→M	missense_variant	COSMIC	—	—	damaging	likely_benign (0.23)	-8.05	COSV99198837
113	K→M	missense_variant	COSMIC	—	—	damaging	likely_benign (0.34)	-8.68	COSV108029107
114	T→N	missense_variant	gnomAD	—	1.37e-06	damaging	likely_benign (0.13)	-7.54	chr19-541422-C-A
114	T→S	missense_variant	gnomAD	—	2.05e-06	—	likely_benign (0.11)	-6.38	chr19-541422-C-G
114	T→T	synonymous_variant	gnomAD	—	6.16e-06	—	—	0.00	chr19-541423-C-A
114	T→T	synonymous_variant	gnomAD	—	1.99e-05	—	—	0.00	chr19-541423-C-G
114	T→T	synonymous_variant	gnomAD	—	3.42e-06	—	—	0.00	chr19-541423-C-T
115	K→Q	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.11)	-7.34	chr19-541424-A-C
115	K→E	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.18)	-6.90	chr19-541424-A-G
116	A→T	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.06)	0.82	chr19-541427-G-A
116	A→S	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.08)	-4.75	chr19-541427-G-T
116	A→G	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.09)	-5.75	chr19-541428-C-G
116	A→V	missense_variant	gnomAD	—	8.90e-06	—	likely_benign (0.07)	-2.84	chr19-541428-C-T
116	A→A	synonymous_variant	gnomAD	—	2.68e-04	—	—	0.00	chr19-541429-G-A
116	A→V	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.07)	-2.84	ClinVar:2556788
116	A→V	missense_variant	COSMIC	—	—	—	likely_benign (0.07)	-2.84	COSV108029109
117	P→A	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.05)	-6.21	chr19-541430-C-G
117	P→L	missense_variant	gnomAD	—	3.36e-05	—	likely_benign (0.07)	-5.14	chr19-541431-C-T
117	P→P	synonymous_variant	gnomAD	—	4.93e-05	—	—	0.00	chr19-541432-G-A
117	P→L	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.07)	-5.14	ClinVar:3998496
117	P→S	missense_variant	COSMIC	—	—	—	likely_benign (0.09)	-5.71	COSV99198836
118	A→T	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.07)	-4.03	chr19-541433-G-A
118	A→G	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.09)	-5.53	chr19-541434-C-G
118	A→V	missense_variant	gnomAD	—	1.16e-05	—	likely_benign (0.06)	-2.34	chr19-541434-C-T
118	A→A	synonymous_variant	gnomAD	—	2.94e-05	—	—	0.00	chr19-541435-G-A
118	A→A	synonymous_variant	gnomAD	—	6.16e-06	—	—	0.00	chr19-541435-G-C
119	P→S	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.07)	-6.10	chr19-541436-C-T
119	P→H	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.09)	-7.57	chr19-541437-C-A
119	—	inframe_deletion	gnomAD	—	1.37e-06	—	—	—	chr19-541437-CCGACGAGGGCTCAGACCTCTTCTACGACGACTACTACGAGGA-C
119	P→P	synonymous_variant	gnomAD	—	1.18e-04	—	—	0.00	chr19-541438-C-T
119	P→P	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99198857
120	D→N	missense_variant	gnomAD	—	2.94e-05	—	likely_benign (0.09)	-7.21	chr19-541439-G-A
120	D→D	synonymous_variant	gnomAD	—	3.29e-05	—	—	0.00	chr19-541441-C-T
120	—	frameshift_variant	gnomAD	—	6.85e-07	LoF	—	—	chr19-541441-CG-C
120	D→N	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.09)	-7.21	ClinVar:2204553
121	E→K	missense_variant	gnomAD	—	1.42e-04	damaging	likely_benign (0.11)	-7.98	chr19-541442-G-A
121	E→G	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.09)	-6.07	chr19-541443-A-G
121	E→D	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.07)	-4.04	chr19-541444-G-C
122	G→V	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.11)	-7.80	chr19-541446-G-T
122	G→G	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-541447-C-T
123	—	frameshift_variant	gnomAD	—	6.85e-07	LoF	—	—	chr19-541448-T-TCAGA
124	D→H	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.25)	-7.65	chr19-541451-G-C
124	D→G	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.16)	-7.08	chr19-541452-A-G
124	D→E	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.15)	-5.90	chr19-541453-C-A
124	D→D	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-541453-C-T
125	L→F	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.11)	-6.56	chr19-541454-C-T
125	L→L	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-541456-C-T
126	—	inframe_deletion	gnomAD	—	4.11e-06	—	—	—	chr19-541458-TCTA-T
126	—	inframe_deletion	gnomAD	—	6.85e-07	—	—	—	chr19-541458-TCTACGACGACTA-T
126	F→L	missense_variant	gnomAD	—	1.37e-06	—	ambiguous (0.53)	-2.31	chr19-541459-C-A
126	F→L	missense_variant	gnomAD	—	5.48e-06	—	ambiguous (0.53)	-2.31	chr19-541459-C-G
126	F→F	synonymous_variant	gnomAD	—	2.05e-06	—	—	0.00	chr19-541459-C-T
126	F→L	missense_variant	ClinVar	Uncertain significance	—	—	ambiguous (0.53)	-2.31	ClinVar:4650833
126	F→S	missense_variant	COSMIC	—	—	damaging	ambiguous (0.46)	-7.78	COSV52741756
127	Y→D	missense_variant	gnomAD	—	4.59e-05	damaging	likely_benign (0.30)	-9.31	chr19-541460-T-G
127	—	inframe_insertion	gnomAD	—	6.85e-07	—	—	—	chr19-541460-T-TACG
127	—	inframe_deletion	gnomAD	—	2.05e-06	—	—	—	chr19-541460-TACG-T
127	Y→C	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.13)	-5.81	chr19-541461-A-G
127	Y→Y	synonymous_variant	gnomAD	—	8.56e-05	—	—	0.00	chr19-541462-C-T
127	Y→D	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_benign (0.30)	-9.31	ClinVar:3998493
128	D→N	missense_variant	gnomAD	—	1.44e-05	damaging	likely_benign (0.24)	-7.54	chr19-541463-G-A
128	D→H	missense_variant	gnomAD	—	1.37e-04	damaging	likely_pathogenic (0.58)	-9.42	chr19-541463-G-C
128	D→G	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.26)	-7.83	chr19-541464-A-G
128	D→D	synonymous_variant	gnomAD	—	1.92e-05	—	—	0.00	chr19-541465-C-T
128	D→H	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_pathogenic (0.58)	-9.42	ClinVar:3488345
128	D→N	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_benign (0.24)	-7.54	ClinVar:3998495
128	D→H	missense_variant	COSMIC	—	—	damaging	likely_pathogenic (0.58)	-9.42	COSV52741959
129	D→N	missense_variant	gnomAD	—	1.37e-06	damaging	likely_benign (0.19)	-7.65	chr19-541466-G-A
129	D→Y	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.28)	-9.31	chr19-541466-G-T
129	—	inframe_deletion	gnomAD	—	1.10e-05	—	—	—	chr19-541466-GACT-G
129	D→V	missense_variant	gnomAD	—	6.85e-07	damaging	ambiguous (0.42)	-10.56	chr19-541467-A-T
129	D→E	missense_variant	gnomAD	—	2.74e-06	—	likely_benign (0.22)	-6.62	chr19-541468-C-A
129	D→D	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-541468-C-T
129	D→Y	missense_variant	COSMIC	—	—	damaging	likely_benign (0.28)	-9.31	COSV52742944
130	Y→D	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.11)	-5.93	chr19-541469-T-G
130	Y→S	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.12)	-9.12	chr19-541470-A-C
130	Y→C	missense_variant	gnomAD	—	4.11e-06	—	likely_benign (0.10)	-6.49	chr19-541470-A-G
130	Y→*	stop_gained	gnomAD	—	6.85e-07	LoF	—	—	chr19-541471-C-G
131	Y→H	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.29)	-9.37	chr19-541472-T-C
131	Y→C	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.10)	-6.93	chr19-541473-A-G
131	Y→F	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.11)	-7.47	chr19-541473-A-T
131	Y→*	stop_gained	gnomAD	—	6.85e-07	LoF	—	—	chr19-541474-C-G
131	Y→Y	synonymous_variant	gnomAD	—	7.54e-06	—	—	0.00	chr19-541474-C-T
131	—	inframe_deletion	gnomAD	—	1.37e-06	—	—	—	chr19-541474-CGAGGACGGCGAGGTGGAG-C
132	E→K	missense_variant	gnomAD	—	7.53e-06	damaging	likely_benign (0.21)	-9.21	chr19-541475-G-A
132	E→*	stop_gained	gnomAD	—	2.74e-06	LoF	—	—	chr19-541475-G-T
132	E→G	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.11)	-7.42	chr19-541476-A-G
132	E→D	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.07)	-3.13	chr19-541477-G-C
132	E→Q	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_benign (0.15)	-10.08	ClinVar:4650834
132	E→K	missense_variant	COSMIC	—	—	damaging	likely_benign (0.21)	-9.21	COSV52742485
133	D→N	missense_variant	gnomAD	—	6.85e-07	damaging	likely_benign (0.12)	-7.62	chr19-541478-G-A
133	D→G	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.11)	-7.40	chr19-541479-A-G
133	D→D	synonymous_variant	gnomAD	—	1.64e-05	—	—	0.00	chr19-541480-C-T
133	D→E	missense_variant	COSMIC	—	—	—	likely_benign (0.10)	-5.59	COSV106053548
133	D→D	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52742617
134	G→S	missense_variant	gnomAD	—	7.54e-06	—	likely_benign (0.07)	-5.11	chr19-541481-G-A
134	G→C	missense_variant	gnomAD	—	2.06e-06	—	likely_benign (0.09)	-6.67	chr19-541481-G-T
134	G→V	missense_variant	gnomAD	—	2.06e-06	—	likely_benign (0.09)	-6.51	chr19-541482-G-T
134	G→G	synonymous_variant	gnomAD	—	7.54e-06	—	—	0.00	chr19-541483-C-T
134	G→S	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.07)	-5.11	ClinVar:3488349
134	G→S	missense_variant	COSMIC	—	—	—	likely_benign (0.07)	-5.11	COSV99198803
134	G→G	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52742106
135	E→K	missense_variant	gnomAD	—	3.43e-06	damaging	likely_benign (0.16)	-8.38	chr19-541484-G-A
135	E→K	missense_variant	COSMIC	—	—	damaging	likely_benign (0.16)	-8.38	COSV99198882
136	V→M	missense_variant	gnomAD	—	4.04e-05	—	likely_benign (0.08)	0.41	chr19-541487-G-A
136	V→E	missense_variant	gnomAD	—	6.85e-07	—	likely_benign (0.07)	-4.47	chr19-541488-T-A
136	—	inframe_insertion	gnomAD	—	6.85e-07	—	—	—	chr19-541488-T-TGGA
136	—	inframe_deletion	gnomAD	—	2.74e-06	—	—	—	chr19-541488-TGGA-T
136	V→V	synonymous_variant	gnomAD	—	6.85e-07	—	—	0.00	chr19-541489-G-A
136	V→M	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.08)	0.41	ClinVar:2357425
136	V→V	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52742478
136	V→V	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV99198828
137	E→K	missense_variant	gnomAD	—	2.06e-06	damaging	likely_benign (0.16)	-8.70	chr19-541490-G-A
138	E→K	missense_variant	gnomAD	—	6.86e-07	damaging	likely_benign (0.14)	-7.84	chr19-541493-G-A
138	E→Q	missense_variant	gnomAD	—	6.86e-07	—	likely_benign (0.12)	-6.71	chr19-541493-G-C
138	E→A	missense_variant	gnomAD	—	2.06e-06	—	likely_benign (0.08)	-0.56	chr19-541494-A-C
138	E→G	missense_variant	gnomAD	—	6.86e-07	—	likely_benign (0.07)	-3.49	chr19-541494-A-G
139	E→K	missense_variant	gnomAD	—	1.47e-04	damaging	likely_benign (0.16)	-8.88	chr19-541496-G-A
139	E→A	missense_variant	gnomAD	—	8.23e-06	—	likely_benign (0.09)	-7.35	chr19-541497-A-C
139	E→E	synonymous_variant	gnomAD	—	1.37e-06	—	—	0.00	chr19-541498-G-A
139	E→K	missense_variant	ClinVar	Uncertain significance	—	damaging	likely_benign (0.16)	-8.88	ClinVar:2410995
140	A→D	missense_variant	gnomAD	—	6.86e-07	—	likely_benign (0.07)	-6.53	chr19-541500-C-A
140	A→V	missense_variant	gnomAD	—	7.55e-06	—	likely_benign (0.08)	-4.25	chr19-541500-C-T
140	A→A	synonymous_variant	gnomAD	—	6.86e-07	—	—	0.00	chr19-541501-C-A
140	A→A	synonymous_variant	gnomAD	—	1.51e-05	—	—	0.00	chr19-541501-C-T
140	A→V	missense_variant	COSMIC	—	—	—	likely_benign (0.08)	-4.25	COSV99198823
140	A→A	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52741776
141	D→N	missense_variant	gnomAD	—	1.17e-05	—	likely_benign (0.09)	-5.71	chr19-541502-G-A
141	D→N	missense_variant	COSMIC	—	—	—	likely_benign (0.09)	-5.71	COSV52742922
142	S→G	missense_variant	gnomAD	—	1.37e-06	—	likely_benign (0.06)	-7.09	chr19-541505-A-G
142	S→S	synonymous_variant	gnomAD	—	6.87e-07	—	—	0.00	chr19-541507-C-T
143	C→R	missense_variant	gnomAD	—	6.87e-07	—	likely_benign (0.25)	-7.05	chr19-541508-T-C
144	F→F	synonymous_variant	gnomAD	—	2.20e-05	—	—	0.00	chr19-541513-C-T
144	F→F	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52743389
145	G→R	missense_variant	gnomAD	—	5.50e-06	—	likely_benign (0.19)	-5.61	chr19-541514-G-A
146	D→N	missense_variant	gnomAD	—	2.06e-06	—	likely_benign (0.09)	-5.66	chr19-541517-G-A
146	D→A	missense_variant	gnomAD	—	6.87e-07	—	likely_benign (0.11)	-5.57	chr19-541518-A-C
146	D→E	missense_variant	gnomAD	—	2.06e-06	—	likely_benign (0.08)	-2.75	chr19-541519-C-G
146	D→D	synonymous_variant	gnomAD	—	2.34e-05	—	—	0.00	chr19-541519-C-T
146	D→E	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.08)	-2.75	ClinVar:3140826
147	D→N	missense_variant	gnomAD	—	4.75e-05	—	likely_benign (0.09)	-4.98	chr19-541520-G-A
147	D→Y	missense_variant	gnomAD	—	6.88e-07	damaging	likely_benign (0.12)	-8.01	chr19-541520-G-T
147	D→G	missense_variant	gnomAD	—	6.88e-07	—	likely_benign (0.09)	-6.07	chr19-541521-A-G
147	D→D	synonymous_variant	gnomAD	—	1.38e-06	—	—	0.00	chr19-541522-T-C
147	D→N	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.09)	-4.98	ClinVar:2231100
147	D→N	missense_variant	COSMIC	—	—	—	likely_benign (0.09)	-4.98	COSV52742065
148	E→*	stop_gained	gnomAD	—	3.99e-05	LoF	—	—	chr19-541523-G-T
148	E→G	missense_variant	gnomAD	—	6.88e-07	—	likely_benign (0.08)	-5.90	chr19-541524-A-G
148	E→E	synonymous_variant	gnomAD	—	1.24e-05	—	—	0.00	chr19-541525-G-A
148	E→E	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52743091
149	D→D	synonymous_variant	gnomAD	—	6.89e-07	—	—	0.00	chr19-541528-T-C
150	D→Y	missense_variant	gnomAD	—	1.38e-06	damaging	likely_benign (0.29)	-8.56	chr19-541529-G-T
150	D→G	missense_variant	gnomAD	—	2.07e-06	—	likely_benign (0.26)	-6.59	chr19-541530-A-G
150	—	frameshift_variant	gnomAD	—	9.67e-06	LoF	—	—	chr19-541530-ACT-A
150	D→D	synonymous_variant	gnomAD	—	6.91e-07	—	—	0.00	chr19-541531-C-T
151	S→T	missense_variant	gnomAD	—	6.91e-07	damaging	likely_benign (0.13)	-8.62	chr19-541532-T-A
151	S→C	missense_variant	gnomAD	—	4.15e-06	damaging	likely_benign (0.16)	-10.25	chr19-541533-C-G
152	G→G	synonymous_variant	gnomAD	—	2.77e-06	—	—	0.00	chr19-541537-C-G
153	T→M	missense_variant	gnomAD	—	9.03e-06	—	likely_benign (0.10)	-6.22	chr19-541539-C-T
153	T→T	synonymous_variant	gnomAD	—	2.78e-06	—	—	0.00	chr19-541540-G-A
153	T→T	synonymous_variant	gnomAD	—	3.91e-04	—	—	0.00	chr19-541540-G-C
153	T→M	missense_variant	ClinVar	Uncertain significance	—	—	likely_benign (0.10)	-6.22	ClinVar:3264958
154	E→*	stop_gained	gnomAD	—	6.95e-07	LoF	—	—	chr19-541541-G-T
154	—	frameshift_variant	gnomAD	—	8.34e-06	LoF	—	—	chr19-541542-AGGAGTCCT-A
154	E→Q	missense_variant	COSMIC	—	—	damaging	likely_benign (0.25)	-8.49	COSV105074697
154	E→E	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52743032
155	E→E	synonymous_variant	gnomAD	—	7.00e-07	—	—	0.00	chr19-541546-G-A
156	S→S	synonymous_variant	gnomAD	—	7.03e-07	—	—	0.00	chr19-541549-C-A
156	S→S	synonymous_variant	COSMIC	—	—	—	—	0.00	COSV52741880

465 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.

CDC34 · ENST00000215574.9

Folding

Evidence — click any tile for the differential-region detail

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Comparison

Elements and coordinates

Below threshold

Comparison

Details

Comparison

Part 1 · Global feature comparison

Isoform-only features — 38 total (prevalence ≥ 2)

Canonical-only features — 391 total (prevalence ≥ 2)

Shared features by |Δ| activation — 719 total (prevalence ≥ 2)

Part 2 · Differential coordinates

Unique-region features — 607 distinct (prevalence ≥ 2)

Clinical variants

Differential region — lost N-terminus (canonical-only)

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