Is ERCC6 p.Ala211Val (c.632C>T) pathogenic?

ERCC6 p.Ala211Val (c.632C>T) is classified Likely benign in ERCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). AlphaMissense: likely benign (0.078); Ultra-rare (popmax 0.02%, afr).

How common is ERCC6 p.Ala211Val (c.632C>T) in the general population?

ERCC6 p.Ala211Val (c.632C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about ERCC6 p.Ala211Val (c.632C>T)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

ERCC6 p.Ala211Val

c.632C>T · rs749319221 · VCV2177792

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.95, phastCons 0.002
Regional constraint	o/e 0.94	unconstrained · MANE · 74 kb · p 0.017 · regional, not allelic
Overall
CADD	11.43	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/74,902 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.00124% 20/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,993
Middle Eastern	0.0164%	6,084
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0032%	31,242

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERCC6
Protein: p.Ala211Val
Coding: c.632C>T
MANE Select: NM_000124
dbSNP: rs749319221
Type: single nucleotide variant
Location: chr10:49528437 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 211: the 'n-terminal domain; essential for its chromatin remodeling activity' region

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

Similar variants

ERCC6 p.Ala211= Likely benign ★ same residue
ERCC6 p.Ala211Thr 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-ala211val (accessed [today's date]).

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