Is ERCC1 p.Ala266= (c.798A>G) pathogenic?

ERCC1 p.Ala266= (c.798A>G) is classified Likely benign in ERCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-14). Very rare (popmax 0.00136%, nfe).

How common is ERCC1 p.Ala266= (c.798A>G) in the general population?

ERCC1 p.Ala266= (c.798A>G) is very rare (popmax 0.00136%, nfe) (gnomAD).

ERCC1 p.Ala266=

c.798A>G · rs772546871 · VCV1922483

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.1	GERP -3.2
Overall
CADD	0.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,180,030 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000992% 16/1,613,708 alleles · very rare

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: ERCC1
Protein: p.Ala266=
Coding: c.798A>G
MANE Select: NM_001983
dbSNP: rs772546871
Type: single nucleotide variant
Location: chr19:45413722 (GRCh38)
Gene constraint: LOEUF 1.306 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 14 PDB
Residue 266: a UniProt-annotated variant site (in); the 'hhh2, dimerization with ercc4/xpf' region

Full ERCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERCC1 p.Ala266Pro Uncertain significance ★ ⚠ same residue
POLR1G p.Asp266Asn Uncertain significance ★ ⚠ same residue
ERCC1 c.526-1G>A Likely pathogenic ★★ same type
ERCC1 p.Arg41Ter Pathogenic ★★ same type
ERCC1 c.843+52A>G Uncertain significance ★★ same type
ERCC1 p.Ala265Thr Uncertain significance ★★ ⚠ same type
ERCC1 p.Arg156Gln Uncertain significance ★★ ⚠ same type
ERCC1 p.Arg207Trp Uncertain significance ★★ 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/ercc1-p-ala266 (accessed [today's date]).

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