SwissIsoform v2

MAD2L1 · ENST00000296509.11

TRUNCATED 175 aa (canonical 205 aa) · UniProt Q13257 · CDLMPS

chr4:120065801:-:ATT:ENST00000296509.11

AI summary Truncation deletes a confidently-folded N-terminal helix docked against the HORMA fold core, though the core domain itself stays intact.
How it diverges

This truncation removes a 23-residue helix (canonical residues 13-35, pLDDT 0.965) that the structural model places in extensive, high-confidence contact with 35 residues spread across the rest of the canonical fold (mean PAE 1.38 Å) — a load-bearing element rather than a peripheral decoration. However, no real InterPro domain boundary falls in this stretch (HORMA domain and Mad2-like signature all begin at residue 8-15 and extend to ~197-205, so the core fold's catalytic/binding architecture is formally retained), and DeepLoc/SignalP/TargetP show no localization or targeting change.

Why it matters

MAD2L1's checkpoint function depends on a conformational switch (open/closed HORMA states) that mediates MAD1 and Cdc20 binding at kinetochores; losing a helix this tightly integrated with the fold's contact network plausibly perturbs that conformational machinery even though the primary HORMA/Mad2-like domain annotation nominally survives. The shared-region RMSD (2.79 Å) that might otherwise support a broader refold claim is not usable here since the isoform's own structural confidence (pTM 0.59, shared pLDDT 0.64) fails the reliability gate, so this reads as a discrete loss of a docked N-terminal helix rather than evidence of whole-core reorganization.

Truncated functional region
LLM confidence medium

Detection of this alternative start is weak (1/6 cell lines, low initiation efficiency, no validated MS peptide) and disease/germline variant signals in the removed region show no real enrichment (all ClinVar hits benign/uncertain, gnomAD depletion ratio tolerant), so confidence rests mainly on the structural contact evidence, not on independent functional-importance corroboration.

Folding

Canonical (205 aa)
Download CIF
Isoform (175 aa)
Download CIF
Coloured by ESMFold2 pLDDT confidence (blue = high, orange/red = low). Differential region — residues 1–31 (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 (1–31).

Evidence — click any tile for the differential-region detail

C Conservation Interesting
LLM reasoning
The 32-aa N-terminal segment removed by this truncation is under strong, near-canonical-level purifying selection, arguing its loss is functionally consequential rather than neutral. Primate amino-acid identity is 99.5% (essentially matching the canonical protein's own 99.7%), mammalian identity is 93.1% (close to canonical's 95.4%), and absolute phyloP over the unique region is 4.08 — well above the ~2 constraint threshold and nearly matching the shared region's 4.30. Together these show this N-terminal stretch has been evolving under selective pressure comparable to the rest of the protein, so its removal in the truncated isoform likely strips away a conserved, functionally relevant element rather than dispensable sequence.
Unique region 99.5% similar across primates
Unique region 93.1% similar across mammals
Unique region PhyloP: 4.08 — purifying selection
D Detection Not interesting
LLM reasoning
Detection of this truncated start site is thin and its usage is minor relative to canonical: it is picked up in only 1 of 6 cell lines (HeLa, q=0.026), and even there the initiation efficiency is just 0.043, only 0.029x the canonical TIS efficiency in the same line (1.50), indicating the downstream start is a minor, rarely-used alternative rather than a dominant isoform-generating event. No cell-line data exist for K562, U2OS, or RPE1 conditions to corroborate breadth. Direct proteomic support is absent: the single isoform-unique peptide identified was not validated by PepQuery2 (0/1), so there is no mass-spec confirmation that the truncated protein is actually produced.
detected in 1/6 cell lines
alt used 0.029× vs canonical
0/1 isoform-unique peptides validated
L Localization Not interesting
LLM reasoning
No localization signal change accompanies loss of this N-terminal 32-residue segment: both isoform and canonical protein are predicted cytoplasmic with matching nuclear export signal and soluble (non-membrane) status, and the top-class probabilities barely shift (0.64 vs 0.66). Sorting-signal predictors likewise show no change — both isoform and canonical score as noTP (no transit peptide) with no signal peptide, and probability deltas are negligible (<0.001). Removal of this N-terminal segment does not appear to alter subcellular targeting in these predictions.
iso: Cytoplasm | canon: Cytoplasm
iso: noTP | canon: noTP
M Mutation Landscape Not interesting
LLM reasoning
Nothing here supports a functional or disease-relevant signal in the removed N-terminal segment. Both germline-constraint signals agree in the tolerant direction (gnomAD depletion ratio 1.70, i.e. more common variation in the unique region than the shared core; ESM-C constraint_enrichment only 0.34, with zero constrained positions in the unique region) — a rare case where the two independent signals concur rather than merely not conflicting. The disease-density enrichment (1.42x) that looked notable in the summary dissolves on inspection: all 7 ClinVar variants in the unique region (canonical residues 6-17) are Uncertain significance or Likely benign — none pathogenic — and the 14 COSMIC records there are essentially all singleton samples (cosmic_sample_count=1, one at 4), showing no recurrent selection, not a validated hotspot. The positional histogram shows only 6 distinct residues hit by 7 variants, a diffuse scatter rather than a tight cluster. AlphaMissense flags a good fraction of the missense calls here as likely-pathogenic (25/47 scored, mean 0.58) but this is an unconfirmed computational prediction with no corroborating clinical or recurrent-somatic evidence, so it does not override the absence of real disease signal.
gnomAD variants 1.70× more in unique region — tolerant
Disease variants 1.42× more in unique region — enriched
P Predicted Structure Interesting
LLM reasoning
The truncation deletes a confidently folded, well-integrated helix from the canonical structure, which is the strongest possible finding for this category. The lost element (canonical residues 13-35, 23 aa, mean pLDDT 0.965) packs against 35 distinct residues spread across multiple regions of the core (near 36-77, 110-145, 188-191), and its predicted aligned error to the rest of the canonical fold averages only 1.38 Å (max 10.44), showing it is not just folded but confidently docked against the body — this is read on the canonical side where pTM is high (0.950) and shared pLDDT is 0.946, so the finding is trustworthy. The isoform-side shared-region RMSD (2.79 Å) is not used as supporting evidence since the isoform's own pTM (0.592) and shared pLDDT (0.637) fail the confidence gate, making that scalar an artifact of placement uncertainty rather than a real conformational change. The core signal here is independent of that gate: a genuine, load-bearing helix is lost by this truncation.
pLDDT Differential Region: 0.896
Shared-Region RMSD: 2.79 Å
1 secondary structure identified in unique region
S Structural Characteristics Not interesting
LLM reasoning
None of the structural-characteristics submodules show a meaningful shift for this truncation. The N-terminal segment removed by this isoform does not overlap any real InterPro domain (all six hits, including the HORMA domain superfamily and Mad2-like signature, sit within the retained region, e.g. positions 8-205), so the core HORMA fold is structurally intact in the truncated protein. Whole-protein biophysical descriptors (gravy, fraction charged, disorder) show only small deltas (-0.09, +0.016, +0.009) that fail to clear the shift threshold. The sparse-autoencoder magnitude check also falls short of its threshold (top shared-feature |delta| 8.00 vs 10.0 required); the large gained/lost counts (12 vs 68) are explicitly context only, not evidence of a real effect, and per the interpretation guidance the feature labels themselves carry no probative weight. Overall, this category gives no support for a functionally consequential structural change from losing this N-terminal stretch.
No diverging domains
more hydrophobic (+0.67) · less charged (-0.11) · less disordered (-0.08)
80 SAE features differ

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
— I→I intronic gnomAD — 6.85e-07 — — 0.00 chr4-120065808-G-A
— I→F intronic gnomAD — 6.85e-07 damaging likely_pathogenic (0.85) -11.62 chr4-120065810-T-A
— G→G intronic gnomAD — 3.63e-05 — — 0.00 chr4-120065811-G-A
— G→D intronic gnomAD — 6.85e-07 damaging likely_pathogenic (1.00) -12.62 chr4-120065812-C-T
— G→S intronic gnomAD — 2.05e-06 damaging likely_pathogenic (0.79) -7.87 chr4-120065813-C-T
— F→F intronic gnomAD — 6.85e-07 — — 0.00 chr4-120065814-G-A
— F→L intronic gnomAD — 8.90e-06 damaging likely_pathogenic (0.99) -8.68 chr4-120065814-G-C
— S→S intronic gnomAD — 6.85e-07 — — 0.00 chr4-120065817-T-A
— S→A intronic gnomAD — 1.38e-06 damaging likely_benign (0.10) -7.52 chr4-120066662-A-C
— — intronic gnomAD — 2.07e-06 damaging — — chr4-120066662-AG-A
— F→F intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066663-G-A
— F→S intronic gnomAD — 2.07e-06 damaging likely_pathogenic (0.99) -14.12 chr4-120066664-A-G
— F→L intronic gnomAD — 6.89e-07 damaging likely_pathogenic (1.00) -10.12 chr4-120066668-A-G
— E→E intronic gnomAD — 8.27e-06 — — 0.00 chr4-120066669-C-T
— A→A intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066672-G-A
— A→T intronic gnomAD — 6.89e-07 damaging likely_pathogenic (0.67) -7.68 chr4-120066674-C-T
— V→A intronic gnomAD — 6.89e-07 damaging likely_pathogenic (0.96) -10.94 chr4-120066676-A-G
— V→L intronic gnomAD — 2.07e-06 damaging likely_pathogenic (0.97) -11.31 chr4-120066677-C-G
— I→M intronic gnomAD — 1.38e-06 — likely_benign (0.16) -7.18 chr4-120066678-G-C
— I→I intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066678-G-T
— E→K intronic gnomAD — 1.38e-06 damaging likely_pathogenic (0.68) -9.80 chr4-120066683-C-T
— A→A intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066684-G-C
— A→A intronic gnomAD — 1.38e-06 — — 0.00 chr4-120066684-G-T
— A→V intronic gnomAD — 6.89e-07 damaging likely_pathogenic (0.92) -8.25 chr4-120066685-G-A
— A→S intronic gnomAD — 6.89e-07 — likely_benign (0.29) -7.50 chr4-120066686-C-A
— A→T intronic gnomAD — 6.89e-07 damaging likely_pathogenic (0.78) -7.62 chr4-120066686-C-T
— G→G intronic gnomAD — 2.75e-06 — — 0.00 chr4-120066690-C-G
— G→G intronic gnomAD — 1.24e-05 — — 0.00 chr4-120066690-C-T
— G→R intronic gnomAD — 6.89e-07 damaging likely_pathogenic (1.00) -10.12 chr4-120066692-C-G
— R→R intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066693-G-T
— L→P intronic gnomAD — 8.95e-06 damaging likely_pathogenic (0.99) -11.44 chr4-120066697-A-G
— L→M intronic gnomAD — 6.89e-07 damaging likely_pathogenic (0.81) -12.94 chr4-120066698-G-T
— T→T intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066699-G-A
— I→M intronic gnomAD — 6.89e-07 damaging likely_pathogenic (0.80) -10.37 chr4-120066702-G-C
— I→T intronic gnomAD — 1.38e-06 damaging likely_pathogenic (0.98) -10.87 chr4-120066703-A-G
— I→V intronic gnomAD — 6.89e-06 — likely_benign (0.28) -7.12 chr4-120066704-T-C
— G→G intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066705-T-C
— G→R intronic gnomAD — 2.76e-06 damaging likely_pathogenic (0.89) -8.56 chr4-120066707-C-T
— Q→Q intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066708-C-T
— E→E intronic gnomAD — 6.89e-07 — — 0.00 chr4-120066711-C-T
— E→V intronic gnomAD — 6.89e-07 damaging likely_benign (0.32) -9.29 chr4-120066712-T-A
— — intronic gnomAD — 6.90e-07 damaging — — chr4-120066712-TC-T
— E→K intronic gnomAD — 4.83e-06 damaging ambiguous (0.44) -8.23 chr4-120066713-C-T
— R→R intronic gnomAD — 4.83e-06 — — 0.00 chr4-120066714-C-T
— R→Q intronic gnomAD — 2.21e-05 — likely_benign (0.17) -6.23 chr4-120066715-C-T
— R→W intronic gnomAD — 6.90e-07 damaging ambiguous (0.52) -8.23 chr4-120066716-G-A
— R→G intronic gnomAD — 1.24e-05 — likely_benign (0.12) -6.55 chr4-120066716-G-C
— S→F intronic gnomAD — 6.90e-07 damaging ambiguous (0.34) -8.62 chr4-120066718-G-A
— L→L intronic gnomAD — 1.38e-06 — — 0.00 chr4-120066720-G-A
— L→L intronic gnomAD — 1.38e-06 — — 0.00 chr4-120066720-G-C
— L→H intronic gnomAD — 1.38e-06 damaging likely_benign (0.14) -8.68 chr4-120066721-A-T
— L→F intronic gnomAD — 3.45e-06 — likely_benign (0.11) -6.81 chr4-120066722-G-A
— L→V intronic gnomAD — 1.38e-06 — likely_benign (0.06) -6.46 chr4-120066722-G-C
— L→I intronic gnomAD — 2.07e-06 — likely_benign (0.07) -6.90 chr4-120066722-G-T
— Q→* intronic gnomAD — 1.38e-06 damaging — — chr4-120066725-G-A
— L→L intronic gnomAD — 6.90e-07 — — 0.00 chr4-120066726-C-T
— A→A intronic gnomAD — 1.38e-06 — — 0.00 chr4-120066729-C-T
— A→V intronic gnomAD — 1.11e-05 damaging likely_pathogenic (0.60) -7.98 chr4-120066730-G-A
— A→E intronic gnomAD — 6.92e-07 damaging ambiguous (0.34) -8.11 chr4-120066730-G-T
— A→S intronic gnomAD — 6.91e-07 — likely_benign (0.13) -5.20 chr4-120066731-C-A
— A→T intronic gnomAD — 1.73e-05 — likely_benign (0.33) -5.05 chr4-120066731-C-T
— M→T intronic gnomAD — 1.38e-06 damaging — -9.37 chr4-120066733-A-G
— M→K intronic gnomAD — 6.92e-07 damaging — -10.81 chr4-120066733-A-T
— M→V intronic gnomAD — 6.92e-07 damaging — -8.87 chr4-120066734-T-C
— G→R intronic ClinVar Uncertain significance — damaging likely_pathogenic (0.89) -8.56 ClinVar:2481387
— I→V intronic ClinVar Uncertain significance — — likely_benign (0.28) -7.12 ClinVar:2490789
— E→E intronic ClinVar Likely benign — — — 0.00 ClinVar:2655056
— L→L intronic ClinVar Likely benign — — — 0.00 ClinVar:2655057
— G→G intronic ClinVar Likely benign — — — 0.00 ClinVar:2655058
— Q→Q intronic ClinVar Likely benign — — — 0.00 ClinVar:2655059
— R→Q intronic ClinVar Uncertain significance — — likely_benign (0.17) -6.23 ClinVar:3541916
— G→G intronic COSMIC — — — — 0.00 COSV56636895
— S→L intronic COSMIC — — damaging likely_benign (0.27) -8.56 COSV56637555
— F→F intronic COSMIC — — — — 0.00 COSV56636758
— F→L intronic COSMIC — — damaging likely_pathogenic (1.00) -10.12 COSV56636790
— E→D intronic COSMIC — — — ambiguous (0.48) -7.37 COSV99633714
— A→V intronic COSMIC — — damaging likely_pathogenic (0.90) -8.81 COSV56637607
— G→R intronic COSMIC — — damaging likely_pathogenic (1.00) -10.12 COSV56637063
— L→M intronic COSMIC — — damaging likely_pathogenic (0.81) -12.94 COSV99633896
— I→I intronic COSMIC — — — — 0.00 COSV106426012
— I→N intronic COSMIC — — damaging likely_pathogenic (0.98) -12.25 COSV56636743
— Q→* intronic COSMIC — — damaging — — COSV56636507
— L→L intronic COSMIC — — — — 0.00 COSV56637843
— L→R intronic COSMIC — — — likely_benign (0.05) -7.25 COSV99633902
— — intronic COSMIC — — damaging — — COSV99634044

85 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
1 L→L synonymous_variant gnomAD — 1.57e-05 — — 0.00 chr4-120065796-T-C
2 Y→* stop_gained gnomAD — 6.84e-07 LoF — — chr4-120065793-A-T
2 Y→H missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.96) -8.81 chr4-120065795-A-G
4 R→H missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.99) -11.31 chr4-120065788-C-T
4 R→C missense_variant COSMIC — — damaging likely_pathogenic (0.99) -11.44 COSV56636453
5 G→G synonymous_variant gnomAD — 2.05e-06 — — 0.00 chr4-120065784-G-C
6 I→M missense_variant gnomAD — 2.05e-06 damaging likely_pathogenic (0.67) -8.43 chr4-120065781-T-C
6 I→V missense_variant gnomAD — 6.84e-07 — likely_benign (0.13) -6.25 chr4-120065783-T-C
6 I→L missense_variant gnomAD — 6.84e-07 — likely_benign (0.23) -7.18 chr4-120065783-T-G
6 I→M missense_variant COSMIC — — damaging likely_pathogenic (0.67) -8.43 COSV56637152
7 Y→S missense_variant gnomAD — 2.05e-06 damaging likely_pathogenic (0.96) -12.62 chr4-120065779-T-G
7 Y→C missense_variant ClinVar Uncertain significance — damaging likely_pathogenic (0.91) -12.06 ClinVar:2337132
8 P→P synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr4-120065775-T-C
9 S→S synonymous_variant gnomAD — 6.84e-06 — — 0.00 chr4-120065772-A-T
9 S→C missense_variant gnomAD — 2.05e-06 damaging likely_benign (0.15) -9.02 chr4-120065773-G-C
11 T→T synonymous_variant gnomAD — 2.05e-06 — — 0.00 chr4-120065766-G-A
11 T→N missense_variant gnomAD — 6.84e-07 damaging likely_benign (0.16) -8.18 chr4-120065767-G-T
13 T→I missense_variant gnomAD — 3.42e-06 — likely_benign (0.26) -6.92 chr4-120065761-G-A
13 T→I missense_variant ClinVar Uncertain significance — — likely_benign (0.26) -6.92 ClinVar:2314971
14 R→G missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.82) -9.50 chr4-120065759-G-C
14 R→R synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr4-120065759-G-T
14 R→* stop_gained COSMIC — — LoF — — COSV56636783
15 V→V synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120065754-C-T
15 V→A missense_variant gnomAD — 6.84e-07 — ambiguous (0.39) -5.87 chr4-120065755-A-G
16 Q→P missense_variant gnomAD — 2.05e-06 damaging likely_benign (0.27) -8.50 chr4-120065752-T-G
16 Q→* stop_gained COSMIC — — LoF — — COSV99634048
16 Q→Q synonymous_variant COSMIC — — — — 0.00 COSV56636984
16 Q→R missense_variant COSMIC — — damaging likely_benign (0.32) -9.25 COSV105896543
17 K→* stop_gained COSMIC — — LoF — — COSV56636610
18 Y→Y synonymous_variant gnomAD — 4.31e-05 — — 0.00 chr4-120065745-G-A
18 Y→C missense_variant COSMIC — — damaging likely_pathogenic (0.98) -9.81 COSV56636603
19 G→R missense_variant COSMIC — — damaging likely_pathogenic (0.97) -10.25 COSV106426007
19 G→* stop_gained COSMIC — — LoF — — COSV56636827
20 L→F missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.91) -9.62 chr4-120065741-G-A
21 T→T synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120065736-G-A
21 T→T synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr4-120065736-G-C
21 T→I missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.77) -8.68 chr4-120065737-G-A
22 L→F missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.77) -9.87 chr4-120065733-C-G
22 — frameshift_variant gnomAD — 8.21e-06 LoF — — chr4-120065733-CA-C
22 L→W missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.98) -13.31 chr4-120065734-A-C
23 L→F missense_variant gnomAD — 6.84e-07 damaging likely_benign (0.26) -8.69 chr4-120065732-G-A
24 V→L missense_variant COSMIC — — — likely_benign (0.32) -7.34 COSV56636970
26 T→A missense_variant gnomAD — 2.12e-05 — likely_benign (0.10) -5.80 chr4-120065723-T-C
29 E→Q missense_variant gnomAD — 6.84e-07 damaging likely_benign (0.13) -7.58 chr4-120065714-C-G
31 — frameshift_variant gnomAD — 6.84e-07 LoF — — chr4-120065708-TG-T
32 K→R missense_variant gnomAD — 6.84e-07 — likely_benign (0.08) -5.92 chr4-120065704-T-C
32 K→* stop_gained gnomAD — 6.84e-07 LoF — — chr4-120065705-T-A
33 Y→F missense_variant gnomAD — 2.74e-06 — ambiguous (0.38) -6.94 chr4-120065701-T-A
33 Y→C missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.96) -10.00 chr4-120065701-T-C
33 Y→N missense_variant COSMIC — — damaging likely_pathogenic (0.98) -10.81 COSV99633708
34 L→L synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120065697-T-C
34 L→L synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120065697-T-G
34 — frameshift_variant gnomAD — 6.84e-07 LoF — — chr4-120065697-TA-T
34 L→I missense_variant gnomAD — 1.21e-04 damaging likely_benign (0.17) -8.31 chr4-120065699-G-T
35 N→S missense_variant gnomAD — 2.74e-06 — likely_benign (0.07) -3.68 chr4-120065695-T-C
35 N→N synonymous_variant COSMIC — — — — 0.00 COSV108109490
36 N→N synonymous_variant gnomAD — 2.05e-06 — — 0.00 chr4-120065691-A-G
36 N→Y missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.16) -8.23 chr4-120065693-T-A
36 N→Y missense_variant ClinVar Uncertain significance — damaging likely_benign (0.16) -8.23 ClinVar:3869470
37 V→G missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.89) -11.56 chr4-120065689-A-C
37 V→L missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.88) -8.69 chr4-120065690-C-A
39 E→K missense_variant COSMIC — — damaging likely_benign (0.14) -7.81 COSV56636425
40 Q→Q synonymous_variant gnomAD — 1.57e-05 — — 0.00 chr4-120065679-T-C
41 L→L synonymous_variant gnomAD — 4.11e-06 — — 0.00 chr4-120065676-C-T
42 K→R missense_variant gnomAD — 6.84e-07 — likely_benign (0.10) -4.08 chr4-120065674-T-C
43 D→G missense_variant gnomAD — 6.88e-07 — likely_benign (0.12) -5.71 chr4-120062095-T-C
43 D→H missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.28) -9.40 chr4-120065672-C-G
44 W→L missense_variant COSMIC — — damaging likely_pathogenic (0.93) -10.50 COSV99633853
45 L→L synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr4-120062088-T-C
45 — frameshift_variant gnomAD — 6.18e-06 LoF — — chr4-120062090-A-AC
46 Y→C missense_variant gnomAD — 2.74e-06 — likely_benign (0.07) -5.45 chr4-120062086-T-C
46 Y→F missense_variant COSMIC — — — likely_benign (0.08) -4.57 COSV56636540
46 Y→H missense_variant COSMIC — — — likely_benign (0.13) -6.64 COSV56637585
47 K→N missense_variant gnomAD — 1.51e-05 — likely_benign (0.19) -6.30 chr4-120062082-C-G
47 K→K synonymous_variant gnomAD — 3.43e-06 — — 0.00 chr4-120062082-C-T
47 K→R missense_variant gnomAD — 1.23e-05 — likely_benign (0.07) -5.96 chr4-120062083-T-C
47 K→* stop_gained COSMIC — — LoF — — COSV56637871
48 C→Y missense_variant gnomAD — 1.37e-06 damaging ambiguous (0.51) -8.62 chr4-120062080-C-T
48 C→S missense_variant gnomAD — 2.06e-06 — ambiguous (0.41) -7.19 chr4-120062081-A-T
49 S→S synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120062076-T-A
49 S→S synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120062076-T-C
49 S→L missense_variant gnomAD — 6.85e-07 — likely_benign (0.10) -6.53 chr4-120062077-G-A
49 S→* stop_gained gnomAD — 6.85e-07 LoF — — chr4-120062077-G-C
49 S→L missense_variant COSMIC — — — likely_benign (0.10) -6.53 COSV56636668
51 Q→R missense_variant gnomAD — 2.06e-06 damaging likely_benign (0.32) -8.62 chr4-120062071-T-C
51 Q→* stop_gained COSMIC — — LoF — — COSV56636702
53 L→L synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120062064-C-A
53 L→L synonymous_variant COSMIC — — — — 0.00 COSV56637689
54 V→V synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120062061-A-T
54 V→F missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.99) -12.31 chr4-120062063-C-A
55 V→L missense_variant gnomAD — 6.85e-07 — likely_benign (0.27) -7.25 chr4-120062060-C-G
55 V→G missense_variant COSMIC — — damaging likely_pathogenic (0.92) -11.81 COSV106426017
56 V→V synonymous_variant gnomAD — 4.79e-06 — — 0.00 chr4-120062055-A-G
56 V→I missense_variant gnomAD — 6.16e-06 damaging likely_benign (0.22) -8.50 chr4-120062057-C-T
57 I→I synonymous_variant gnomAD — 4.11e-06 — — 0.00 chr4-120062052-G-A
57 I→T missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.98) -8.56 chr4-120062053-A-G
59 N→D missense_variant gnomAD — 6.16e-06 — likely_benign (0.07) -6.80 chr4-120062048-T-C
59 N→D missense_variant ClinVar Uncertain significance — — likely_benign (0.07) -6.80 ClinVar:3121965
60 I→V missense_variant gnomAD — 6.09e-05 — likely_benign (0.06) -4.88 chr4-120062045-T-C
60 I→N missense_variant COSMIC — — damaging likely_benign (0.31) -8.57 COSV56636977
60 I→V missense_variant COSMIC — — — likely_benign (0.06) -4.88 COSV99047961
62 S→R missense_variant gnomAD — 6.85e-07 damaging ambiguous (0.48) -9.10 chr4-120062037-A-C
62 S→S synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120062037-A-G
62 S→T missense_variant gnomAD — 6.85e-07 — likely_benign (0.06) -3.75 chr4-120062038-C-G
62 S→N missense_variant gnomAD — 1.16e-05 — likely_benign (0.07) -5.35 chr4-120062038-C-T
62 S→R missense_variant COSMIC — — damaging ambiguous (0.48) -9.10 COSV56636802
63 G→V missense_variant gnomAD — 6.85e-07 damaging ambiguous (0.40) -10.24 chr4-120062035-C-A
63 G→D missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.21) -8.74 chr4-120062035-C-T
64 E→K missense_variant gnomAD — 1.44e-05 damaging likely_benign (0.33) -9.75 chr4-120062033-C-T
64 E→K missense_variant COSMIC — — damaging likely_benign (0.33) -9.75 COSV105174397
65 V→V synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120062028-G-A
66 L→L synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120062025-C-T
66 L→V missense_variant gnomAD — 6.84e-07 damaging likely_benign (0.15) -8.75 chr4-120062027-G-C
68 R→I missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.99) -13.75 chr4-120062020-C-A
70 Q→R missense_variant gnomAD — 2.74e-06 damaging likely_pathogenic (0.85) -10.81 chr4-120062014-T-C
70 Q→P missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.99) -12.12 chr4-120062014-T-G
71 F→L missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (1.00) -10.44 chr4-120062012-A-G
72 D→V missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.81) -10.75 chr4-120062008-T-A
72 D→N missense_variant COSMIC — — damaging ambiguous (0.38) -9.00 COSV109419265
73 I→I synonymous_variant gnomAD — 4.11e-06 — — 0.00 chr4-120062004-A-T
73 I→T missense_variant gnomAD — 3.42e-06 damaging likely_pathogenic (0.79) -9.06 chr4-120062005-A-G
74 E→Q missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.18) -7.62 chr4-120062003-C-G
75 C→Y missense_variant gnomAD — 2.74e-06 damaging likely_pathogenic (0.82) -9.50 chr4-120061999-C-T
76 D→E missense_variant gnomAD — 2.06e-06 damaging likely_pathogenic (0.61) -8.56 chr4-120061995-G-C
77 K→M missense_variant COSMIC — — damaging ambiguous (0.41) -9.25 COSV56637840
78 T→T synonymous_variant gnomAD — 1.24e-05 — — 0.00 chr4-120061989-A-G
78 T→T synonymous_variant COSMIC — — — — 0.00 COSV56637816
79 A→A synonymous_variant gnomAD — 6.88e-07 — — 0.00 chr4-120061986-T-G
79 A→V missense_variant gnomAD — 6.89e-07 — likely_benign (0.10) -5.11 chr4-120061987-G-A
79 A→S missense_variant gnomAD — 2.07e-06 — likely_benign (0.12) -7.11 chr4-120061988-C-A
79 A→V missense_variant COSMIC — — — likely_benign (0.10) -5.11 COSV56636463
80 K→E missense_variant gnomAD — 1.38e-06 damaging likely_benign (0.13) -7.83 chr4-120061985-T-C
81 D→D synonymous_variant gnomAD — 6.90e-07 — — 0.00 chr4-120061980-A-G
81 D→Y missense_variant gnomAD — 3.45e-06 damaging likely_benign (0.26) -8.36 chr4-120061982-C-A
82 D→Y missense_variant gnomAD — 6.90e-07 damaging likely_benign (0.19) -7.57 chr4-120061979-C-A
83 S→S synonymous_variant gnomAD — 5.60e-06 — — 0.00 chr4-120060977-A-G
83 S→I missense_variant ClinVar — — damaging likely_benign (0.15) -7.89 ClinVar:4301842
83 S→N missense_variant COSMIC — — — likely_benign (0.12) -5.11 COSV105174411
84 A→A synonymous_variant gnomAD — 1.39e-06 — — 0.00 chr4-120060974-T-C
84 A→V missense_variant gnomAD — 2.79e-06 — likely_benign (0.07) -3.28 chr4-120060975-G-A
84 A→A synonymous_variant COSMIC — — — — 0.00 COSV56636648
85 P→L missense_variant gnomAD — 2.08e-06 — likely_benign (0.25) -6.75 chr4-120060972-G-A
85 P→A missense_variant gnomAD — 1.39e-06 damaging likely_benign (0.13) -7.56 chr4-120060973-G-C
85 P→T missense_variant COSMIC — — damaging likely_benign (0.21) -7.84 COSV99633915
86 R→S missense_variant gnomAD — 6.89e-07 damaging likely_pathogenic (0.92) -8.87 chr4-120060968-T-A
86 R→I missense_variant gnomAD — 6.92e-07 damaging likely_pathogenic (0.76) -10.80 chr4-120060969-C-A
86 R→G missense_variant gnomAD — 2.07e-06 damaging likely_pathogenic (0.70) -7.90 chr4-120060970-T-C
88 K→K synonymous_variant gnomAD — 6.87e-07 — — 0.00 chr4-120060962-C-T
88 — frameshift_variant gnomAD — 6.87e-07 LoF — — chr4-120060962-CT-C
88 K→M missense_variant gnomAD — 1.99e-05 damaging likely_pathogenic (0.82) -10.31 chr4-120060963-T-A
88 K→E missense_variant gnomAD — 6.88e-07 damaging likely_pathogenic (0.96) -11.06 chr4-120060964-T-C
89 S→S synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120060959-A-G
89 S→F missense_variant gnomAD — 5.70e-05 damaging likely_pathogenic (0.80) -9.05 chr4-120060960-G-A
89 S→C missense_variant gnomAD — 1.37e-06 — likely_benign (0.21) -7.18 chr4-120060960-G-C
89 S→C missense_variant ClinVar Uncertain significance — — likely_benign (0.21) -7.18 ClinVar:2624283
90 Q→H missense_variant gnomAD — 2.06e-06 — likely_benign (0.21) -6.53 chr4-120060956-C-G
90 Q→P missense_variant gnomAD — 3.29e-05 — likely_benign (0.10) -7.21 chr4-120060957-T-G
91 K→K synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr4-120060953-T-C
91 K→T missense_variant gnomAD — 6.86e-07 damaging ambiguous (0.37) -8.37 chr4-120060954-T-G
91 K→E missense_variant gnomAD — 6.86e-07 damaging ambiguous (0.42) -7.78 chr4-120060955-T-C
94 Q→R missense_variant gnomAD — 3.43e-06 damaging likely_benign (0.30) -9.00 chr4-120060945-T-C
94 Q→* stop_gained COSMIC — — LoF — — COSV99633770
95 D→N missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.15) -8.18 chr4-120060943-C-T
95 D→N missense_variant ClinVar Uncertain significance — damaging likely_benign (0.15) -8.18 ClinVar:3121966
97 I→V missense_variant gnomAD — 2.06e-06 damaging likely_pathogenic (0.65) -9.37 chr4-120060937-T-C
97 I→I synonymous_variant COSMIC — — — — 0.00 COSV56637007
97 I→V missense_variant COSMIC — — damaging likely_pathogenic (0.65) -9.37 COSV56636872
98 R→L missense_variant gnomAD — 2.06e-06 damaging likely_pathogenic (0.96) -10.50 chr4-120060933-C-A
98 R→H missense_variant gnomAD — 6.85e-06 damaging likely_pathogenic (0.74) -8.75 chr4-120060933-C-T
98 R→C missense_variant gnomAD — 3.43e-05 damaging likely_pathogenic (0.61) -8.56 chr4-120060934-G-A
98 R→G missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.86) -10.06 chr4-120060934-G-C
98 R→S missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.93) -9.37 chr4-120060934-G-T
98 R→C missense_variant COSMIC — — damaging likely_pathogenic (0.61) -8.56 COSV99633932
99 S→A missense_variant gnomAD — 6.85e-07 — likely_benign (0.12) -6.47 chr4-120060931-A-C
99 S→* stop_gained COSMIC — — LoF — — COSV56636444
100 V→V synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120060926-C-G
101 I→M missense_variant gnomAD — 8.22e-06 damaging likely_benign (0.27) -8.94 chr4-120060923-G-C
102 R→K missense_variant COSMIC — — damaging likely_pathogenic (0.79) -10.37 COSV56637106
102 R→T missense_variant COSMIC — — damaging likely_pathogenic (1.00) -13.44 COSV56636656
103 Q→Q synonymous_variant COSMIC — — — — 0.00 COSV56637581
105 T→T synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr4-120060911-T-C
105 T→I missense_variant COSMIC — — damaging likely_pathogenic (0.94) -9.81 COSV56637834
106 A→A synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr4-120060908-A-C
106 A→D missense_variant COSMIC — — damaging likely_pathogenic (1.00) -11.12 COSV56637574
107 T→T synonymous_variant gnomAD — 1.10e-05 — — 0.00 chr4-120060905-C-T
107 T→M missense_variant gnomAD — 2.06e-06 damaging likely_pathogenic (0.69) -9.56 chr4-120060906-G-A
107 T→T synonymous_variant COSMIC — — — — 0.00 COSV56637199
107 T→M missense_variant COSMIC — — damaging likely_pathogenic (0.69) -9.56 COSV99633752
108 V→V synonymous_variant gnomAD — 6.87e-07 — — 0.00 chr4-120060902-C-T
108 V→V synonymous_variant COSMIC — — — — 0.00 COSV56637231
108 V→A missense_variant COSMIC — — damaging likely_pathogenic (0.97) -10.50 COSV56637826
112 P→P synonymous_variant gnomAD — 6.18e-02 — — 0.00 chr4-120060890-T-C
112 P→L missense_variant gnomAD — 6.89e-07 damaging likely_pathogenic (0.99) -11.69 chr4-120060891-G-A
112 P→P synonymous_variant COSMIC — — — — 0.00 COSV56636944
113 L→L synonymous_variant gnomAD — 6.89e-07 — — 0.00 chr4-120060887-C-G
115 E→D missense_variant COSMIC — — — likely_benign (0.09) -6.00 COSV56637746
115 E→Q missense_variant COSMIC — — damaging likely_benign (0.34) -8.68 COSV56636515
116 V→A missense_variant gnomAD — 6.91e-07 — likely_benign (0.09) -3.35 chr4-120060879-A-G
116 V→F missense_variant gnomAD — 6.91e-07 damaging likely_benign (0.17) -8.22 chr4-120060880-C-A
117 S→F missense_variant gnomAD — 6.92e-07 damaging likely_benign (0.33) -8.87 chr4-120060876-G-A
117 S→Y missense_variant gnomAD — 1.38e-06 damaging likely_benign (0.29) -9.62 chr4-120060876-G-T
117 — frameshift_variant gnomAD — 6.92e-07 LoF — — chr4-120060876-GA-G
118 C→Y missense_variant gnomAD — 3.45e-06 damaging likely_pathogenic (0.97) -10.19 chr4-120060290-C-T
118 C→Y missense_variant ClinVar Uncertain significance — damaging likely_pathogenic (0.97) -10.19 ClinVar:4050418
118 C→R missense_variant COSMIC — — damaging likely_pathogenic (0.98) -11.37 COSV56637100
119 S→L missense_variant gnomAD — 6.88e-07 damaging ambiguous (0.39) -9.55 chr4-120060287-G-A
119 S→* stop_gained COSMIC — — LoF — — COSV56637188
121 D→E missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.91) -8.31 chr4-120060280-A-T
121 D→N missense_variant COSMIC — — damaging likely_pathogenic (0.70) -9.06 COSV108814783
122 L→L synonymous_variant gnomAD — 2.06e-06 — — 0.00 chr4-120060277-C-T
122 L→P missense_variant gnomAD — 2.06e-06 damaging likely_pathogenic (1.00) -11.37 chr4-120060278-A-G
123 L→L synonymous_variant gnomAD — 2.06e-05 — — 0.00 chr4-120060274-C-T
123 L→V missense_variant gnomAD — 2.06e-06 damaging likely_pathogenic (0.82) -9.62 chr4-120060276-G-C
124 — frameshift_variant COSMIC — — LoF — — COSV99633904
125 Y→D missense_variant gnomAD — 6.86e-07 damaging likely_pathogenic (0.99) -11.12 chr4-120060270-A-C
126 T→I missense_variant gnomAD — 6.86e-07 damaging likely_pathogenic (0.96) -6.87 chr4-120060266-G-A
126 T→A missense_variant gnomAD — 6.85e-07 — ambiguous (0.36) -6.75 chr4-120060267-T-C
126 T→A missense_variant COSMIC — — — ambiguous (0.36) -6.75 COSV56637751
128 — frameshift_variant gnomAD — 4.11e-06 LoF — — chr4-120060260-TTGTC-T
129 D→H missense_variant gnomAD — 4.11e-06 damaging likely_pathogenic (0.68) -8.75 chr4-120060258-C-G
130 L→F missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.33) -8.37 chr4-120060253-C-G
130 L→S missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.29) -8.87 chr4-120060254-A-G
130 L→M missense_variant gnomAD — 2.05e-06 — likely_benign (0.10) -7.28 chr4-120060255-A-T
130 L→F missense_variant COSMIC — — damaging likely_benign (0.33) -8.37 COSV99633667
130 L→W missense_variant COSMIC — — damaging likely_pathogenic (0.59) -11.50 COSV56636532
131 V→V synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr4-120060250-A-T
131 V→L missense_variant gnomAD — 7.53e-06 — likely_benign (0.11) -5.09 chr4-120060252-C-G
132 V→V synonymous_variant gnomAD — 4.79e-06 — — 0.00 chr4-120060247-T-C
132 V→L missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.61) -8.00 chr4-120060249-C-A
134 — frameshift_variant COSMIC — — LoF — — COSV56637918
134 — frameshift_variant COSMIC — — LoF — — COSV56637019
134 E→* stop_gained COSMIC — — LoF — — COSV99633990
136 W→S missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (1.00) -12.37 chr4-120060236-C-G
136 W→G missense_variant COSMIC — — damaging likely_pathogenic (0.98) -11.81 COSV56637715
137 E→K missense_variant COSMIC — — damaging likely_pathogenic (0.75) -9.25 COSV99633670
138 E→K missense_variant gnomAD — 2.74e-06 damaging likely_pathogenic (0.92) -9.69 chr4-120060231-C-T
139 S→S synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120060226-C-A
139 S→S synonymous_variant gnomAD — 1.57e-05 — — 0.00 chr4-120060226-C-T
139 S→L missense_variant COSMIC — — damaging likely_pathogenic (0.69) -10.25 COSV104613725
140 G→E missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.89) -9.12 chr4-120060224-C-T
141 — frameshift_variant gnomAD — 6.85e-07 LoF — — chr4-120060220-TG-T
141 P→T missense_variant gnomAD — 9.58e-06 damaging likely_pathogenic (0.89) -10.31 chr4-120060222-G-T
141 P→T missense_variant COSMIC — — damaging likely_pathogenic (0.89) -10.31 COSV56637625
143 F→L missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.77) -6.34 chr4-120060216-A-G
144 I→I synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120060211-A-T
144 I→V missense_variant gnomAD — 4.11e-06 — likely_benign (0.13) -6.56 chr4-120060213-T-C
145 T→T synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120060208-G-A
145 T→T synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120060208-G-C
146 N→N synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120060205-A-G
146 N→S missense_variant gnomAD — 6.85e-07 — likely_benign (0.07) -4.55 chr4-120060206-T-C
147 S→F missense_variant gnomAD — 3.42e-06 damaging likely_pathogenic (0.85) -10.37 chr4-120060203-G-A
147 S→A missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.10) -9.31 chr4-120060204-A-C
147 S→T missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.33) -10.69 chr4-120060204-A-T
148 E→G missense_variant gnomAD — 1.51e-05 damaging likely_pathogenic (0.86) -10.19 chr4-120060200-T-C
149 E→G missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.73) -9.69 chr4-120060197-T-C
149 E→K missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.73) -9.00 chr4-120060198-C-T
150 V→I missense_variant gnomAD — 6.85e-07 damaging ambiguous (0.49) -9.00 chr4-120060195-C-T
151 R→L missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.76) -8.18 chr4-120060191-C-A
151 R→H missense_variant gnomAD — 7.53e-06 — likely_benign (0.32) -6.15 chr4-120060191-C-T
151 R→C missense_variant gnomAD — 1.64e-05 — ambiguous (0.44) -6.15 chr4-120060192-G-A
151 R→L missense_variant COSMIC — — damaging likely_pathogenic (0.76) -8.18 COSV99633797
151 R→C missense_variant COSMIC — — — ambiguous (0.44) -6.15 COSV56637784
152 L→F missense_variant gnomAD — 1.10e-05 damaging likely_pathogenic (0.90) -9.69 chr4-120060189-G-A
152 L→R missense_variant COSMIC — — damaging likely_pathogenic (0.99) -13.06 COSV99633921
153 R→L missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.97) -10.50 chr4-120060185-C-A
153 R→H missense_variant gnomAD — 7.53e-06 damaging likely_pathogenic (0.71) -8.25 chr4-120060185-C-T
153 R→C missense_variant gnomAD — 2.74e-06 damaging likely_pathogenic (0.86) -8.19 chr4-120060186-G-A
153 R→H missense_variant ClinVar Uncertain significance — damaging likely_pathogenic (0.71) -8.25 ClinVar:3541917
153 R→C missense_variant COSMIC — — damaging likely_pathogenic (0.86) -8.19 COSV56637566
154 S→S synonymous_variant gnomAD — 9.59e-06 — — 0.00 chr4-120060181-T-C
154 S→L missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.86) -12.12 chr4-120060182-G-A
154 S→* stop_gained COSMIC — — LoF — — COSV99633830
155 F→F synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr4-120060178-A-G
155 F→L missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (1.00) -9.62 chr4-120060180-A-G
158 T→I missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.89) -7.96 chr4-120060170-G-A
158 T→I missense_variant COSMIC — — damaging likely_pathogenic (0.89) -7.96 COSV106096082
159 I→V missense_variant gnomAD — 5.62e-03 — likely_benign (0.10) -5.18 chr4-120060168-T-C
159 I→V missense_variant ClinVar Benign — — likely_benign (0.10) -5.18 ClinVar:782943
160 H→H synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr4-120060163-G-A
160 H→R missense_variant COSMIC — — damaging likely_pathogenic (0.99) -11.31 COSV56637130
162 V→V synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr4-120060157-T-C
163 N→N synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr4-120060154-A-G
164 S→N missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.93) -10.75 chr4-120060152-C-T
164 S→G missense_variant COSMIC — — damaging likely_benign (0.28) -9.44 COSV56636733
165 M→K missense_variant gnomAD — 7.56e-06 damaging ambiguous (0.44) -9.44 chr4-120060149-A-T
166 V→M missense_variant COSMIC — — damaging likely_pathogenic (1.00) -11.62 COSV56636857
167 A→A synonymous_variant gnomAD — 2.07e-06 — — 0.00 chr4-120060142-G-A
167 A→A synonymous_variant gnomAD — 6.91e-07 — — 0.00 chr4-120060142-G-C
167 A→V missense_variant gnomAD — 6.91e-07 damaging likely_pathogenic (0.78) -8.25 chr4-120060143-G-A
167 A→T missense_variant gnomAD — 2.07e-06 — ambiguous (0.42) -6.56 chr4-120060144-C-T
168 Y→Y synonymous_variant gnomAD — 6.90e-07 — — 0.00 chr4-120060139-G-A
169 K→R missense_variant gnomAD — 2.07e-06 — likely_benign (0.06) -5.31 chr4-120060137-T-C
169 K→E missense_variant gnomAD — 6.90e-07 damaging likely_pathogenic (0.69) -11.37 chr4-120060138-T-C
170 I→M missense_variant gnomAD — 2.07e-06 — likely_benign (0.09) -6.84 chr4-120060133-A-C
170 I→I synonymous_variant gnomAD — 6.90e-07 — — 0.00 chr4-120060133-A-G
171 P→S missense_variant COSMIC — — — likely_benign (0.13) -5.24 COSV56636813
172 V→V synonymous_variant gnomAD — 6.91e-07 — — 0.00 chr4-120060127-G-A
172 V→L missense_variant gnomAD — 4.15e-06 — likely_benign (0.09) -5.62 chr4-120060129-C-G
172 V→I missense_variant gnomAD — 4.84e-06 — likely_benign (0.07) -4.18 chr4-120060129-C-T
172 V→I missense_variant COSMIC — — — likely_benign (0.07) -4.18 COSV56636962
173 N→S missense_variant gnomAD — 1.38e-06 — likely_benign (0.06) -3.94 chr4-120060125-T-C
174 D→D synonymous_variant gnomAD — 1.38e-05 — — 0.00 chr4-120060121-G-A
174 D→Y missense_variant gnomAD — 1.38e-06 damaging likely_benign (0.28) -7.90 chr4-120060123-C-A
174 D→N missense_variant gnomAD — 2.77e-06 — likely_benign (0.08) -6.37 chr4-120060123-C-T
174 D→N missense_variant ClinVar Uncertain significance — — likely_benign (0.08) -6.37 ClinVar:2539636

305 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.

Evidence