Is ERCC3 p.Met590Arg (c.1769T>G) pathogenic?

ERCC3 p.Met590Arg (c.1769T>G) is classified Benign in ERCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely pathogenic (0.9764); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with ERCC3 p.Met590Arg (c.1769T>G)?

ERCC3 p.Met590Arg (c.1769T>G) is associated with ovarian cancer (ClinVar).

How common is ERCC3 p.Met590Arg (c.1769T>G) in the general population?

ERCC3 p.Met590Arg (c.1769T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC3 p.Met590Arg (c.1769T>G)?

AlphaMissense predicts likely pathogenic (score 0.9764) — an in-silico prediction, not a clinical call.

ERCC3 p.Met590Arg

c.1769T>G · rs2468030559 · VCV2445410

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9764 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.9764	likely pathogenic
REVEL	0.704	pathogenic-leaning
SaProt	LLR -16.04	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 36 kb · p 4.8e-07 · regional, not allelic
Overall
CADD	25.9	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

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: ERCC3
Protein: p.Met590Arg
Coding: c.1769T>G
MANE Select: NM_000122
dbSNP: rs2468030559
Type: single nucleotide variant
Location: chr2:127272923 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB
Residue 590: the helicase c-terminal domain; an α-helix

Full ERCC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERCC3 p.Ile156Val Likely pathogenic ★ ⚠ same condition
ERCC3 p.Arg360His Conflicting classifications of pathogenicity ★ ⚠ same condition
ERCC3 p.Arg530Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
ERCC3 p.Glu424Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
ERCC3 p.Ala423Thr Benign ★ ⚠ same condition
ERCC3 p.Lys12Asn Benign ★ ⚠ same condition
ERCC3 c.1828-1G>C Likely pathogenic ★★ same type
ERCC3 c.471+1G>A 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/ercc3-p-met590arg (accessed [today's date]).

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