Is ERCC3 p.Arg360His (c.1079G>A) pathogenic?

ERCC3 p.Arg360His (c.1079G>A) is classified Conflicting classifications of pathogenicity in ERCC3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-01-13). AlphaMissense: likely pathogenic (0.6645); Very rare (popmax 0.0022%, sas); Associated with ovarian cancer.

What condition is associated with ERCC3 p.Arg360His (c.1079G>A)?

ERCC3 p.Arg360His (c.1079G>A) is associated with ovarian cancer (ClinVar).

How common is ERCC3 p.Arg360His (c.1079G>A) in the general population?

ERCC3 p.Arg360His (c.1079G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ERCC3 p.Arg360His (c.1079G>A)?

AlphaMissense predicts likely pathogenic (score 0.6645) — an in-silico prediction, not a clinical call.

ERCC3 p.Arg360His

c.1079G>A · rs764062606 · VCV1395194

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6645 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.6645	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -13.13	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 36 kb · p 4.8e-07 · regional, not allelic
Overall
CADD	28.9	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

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000372% 6/1,613,878 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
African / African-American	0.00133%	74,934
European (non-Finnish)	0.000254%	393,343

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: ERCC3
Protein: p.Arg360His
Coding: c.1079G>A
MANE Select: NM_000122
dbSNP: rs764062606
Type: single nucleotide variant
Location: chr2:127286966 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB
Residue 360: the helicase atp-binding domain

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.Arg360Cys Uncertain significance ★★ ⚠ same residue
ERCC3 p.Ile156Val Likely pathogenic ★ ⚠ 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 p.Met590Arg Benign ★ same condition
ERCC3 c.1828-1G>C 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/ercc3-p-arg360his (accessed [today's date]).

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