Is ERCC2 p.Ala108= (c.324T>G) pathogenic?

ERCC2 p.Ala108= (c.324T>G) is classified Likely benign in ERCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). Absent from gnomAD v4.1.

How common is ERCC2 p.Ala108= (c.324T>G) in the general population?

ERCC2 p.Ala108= (c.324T>G) is absent from gnomAD v4.1 (gnomAD).

ERCC2 p.Ala108=

c.324T>G · rs904303845 · VCV2831288

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.18	GERP -3.3, phastCons 0.004
Overall
CADD	8.418	PHRED · no single calibrated threshold — expert panels disagree

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: ERCC2
Protein: p.Ala108=
Coding: c.324T>G
MANE Select: NM_000400
dbSNP: rs904303845
Type: single nucleotide variant
Location: chr19:45368666 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 108: the helicase atp-binding domain; a β-strand

Full ERCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same residue
ERCC2 p.Ala108Gly Uncertain significance ★ ⚠ same residue
ERCC2 p.Ala108Ser Uncertain significance ★ ⚠ same residue
ERCC2 p.Ala108Val Uncertain significance ★ ⚠ same residue
ERCC2 c.1238-1G>C Likely pathogenic ★★ same type
ERCC2 c.1308-2A>G Likely pathogenic ★★ same type
ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same type
ERCC2 c.1479+2T>C 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/ercc2-p-ala108 (accessed [today's date]).

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