Is ERCC6 p.Ala944Val (c.2831C>T) pathogenic?

ERCC6 p.Ala944Val (c.2831C>T) is classified Uncertain significance in ERCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). AlphaMissense: likely pathogenic (0.9691); Absent from gnomAD v4.1.

How common is ERCC6 p.Ala944Val (c.2831C>T) in the general population?

ERCC6 p.Ala944Val (c.2831C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC6 p.Ala944Val (c.2831C>T)?

AlphaMissense predicts likely pathogenic (score 0.9691) — an in-silico prediction, not a clinical call.

ERCC6 p.Ala944Val

c.2831C>T · rs1850797900 · VCV2050127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9691 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9691	likely pathogenic · top 7% in ERCC6
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -13.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 74 kb · p 0.017 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERCC6
Protein: p.Ala944Val
Coding: c.2831C>T
MANE Select: NM_000124
dbSNP: rs1850797900
Type: single nucleotide variant
Location: chr10:49472469 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 944: an α-helix; the helicase c-terminal domain

Full ERCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERCC6 p.Ala944Thr Uncertain significance ★ ⚠ same residue
ERCC6 p.Ala944= Likely benign same residue
ERCC6 c.1397+1G>C Likely pathogenic ★★ same type
ERCC6 c.1526+1G>T Pathogenic/Likely pathogenic ★★ same type
ERCC6 c.2169+1G>A Likely pathogenic ★★ same type
ERCC6 c.2170-1G>A Pathogenic/Likely pathogenic ★★ same type
ERCC6 c.2286+1G>A Pathogenic/Likely pathogenic ★★ same type
ERCC6 c.2287-2A>G Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ercc6-p-ala944val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown