Is ERCC8 p.Val97Asp (c.290T>A) pathogenic?

ERCC8 p.Val97Asp (c.290T>A) is classified Uncertain significance in ERCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely pathogenic (0.6451); Very rare (popmax 0.00334%, amr).

How common is ERCC8 p.Val97Asp (c.290T>A) in the general population?

ERCC8 p.Val97Asp (c.290T>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ERCC8 p.Val97Asp (c.290T>A)?

AlphaMissense predicts likely pathogenic (score 0.6451) — an in-silico prediction, not a clinical call.

ERCC8 p.Val97Asp

c.290T>A · rs1218258334 · VCV1956687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6451 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6451	likely pathogenic
REVEL	0.401	indeterminate
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 70 kb · p 0.027 · regional, not allelic
Overall
CADD	25.0	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 0.00334% Admixed American · 2/59,838 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000137% 2/1,458,414 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: ERCC8
Protein: p.Val97Asp
Coding: c.290T>A
dbSNP: rs1218258334
Type: single nucleotide variant
Location: chr5:60918374 (GRCh38)

Full ERCC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ercc8-p-val97asp (accessed [today's date]).

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