Is ERCC3 p.Phe89Val (c.265T>G) pathogenic?

ERCC3 p.Phe89Val (c.265T>G) is classified Uncertain significance in ERCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely pathogenic (0.7161); Very rare (popmax 0.00322%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ERCC3 p.Phe89Val (c.265T>G)?

ERCC3 p.Phe89Val (c.265T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ERCC3 p.Phe89Val (c.265T>G) in the general population?

ERCC3 p.Phe89Val (c.265T>G) is very rare (popmax 0.00322%, nfe) (gnomAD).

What do computational predictors say about ERCC3 p.Phe89Val (c.265T>G)?

AlphaMissense predicts likely pathogenic (score 0.7161) — an in-silico prediction, not a clinical call.

ERCC3 p.Phe89Val

c.265T>G · rs1004141219 · VCV2253809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7161	likely pathogenic
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -15.29	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 2.4, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,179,872 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00254% 41/1,613,486 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,049
African / African-American	0.00267%	37,463
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Phe89Val
Coding: c.265T>G
MANE Select: NM_000122
dbSNP: rs1004141219
Type: single nucleotide variant
Location: chr2:127292816 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERCC3 p.Gln711Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Ala120Val Uncertain significance ★★ ⚠ same condition
ERCC3 p.Arg109Gln Uncertain significance ★★ ⚠ same condition
ERCC3 p.Arg283His Uncertain significance ★★ ⚠ same condition
ERCC3 p.Arg334His Uncertain significance ★★ ⚠ same condition
ERCC3 p.Arg453Lys Uncertain significance ★★ ⚠ same condition
ERCC3 p.Arg634Cys Uncertain significance ★★ ⚠ same condition
ERCC3 p.Arg743Cys Uncertain significance ★★ ⚠ same condition

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-phe89val (accessed [today's date]).

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