Is ERCC5 p.Ala1007Gly (c.3020C>G) pathogenic?

ERCC5 p.Ala1007Gly (c.3020C>G) is classified Uncertain significance in ERCC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: likely benign (0.0973); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ERCC5 p.Ala1007Gly (c.3020C>G)?

ERCC5 p.Ala1007Gly (c.3020C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ERCC5 p.Ala1007Gly (c.3020C>G) in the general population?

ERCC5 p.Ala1007Gly (c.3020C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC5 p.Ala1007Gly (c.3020C>G)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

ERCC5 p.Ala1007Gly

c.3020C>G · rs776583974 · VCV1692187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP 1.5, phastCons 0.005
Regional constraint	o/e 1.05	unconstrained · MANE · 7,648 bp · p 0.37 · regional, not allelic
Overall
CADD	19.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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: ERCC5
Protein: p.Ala1007Gly
Coding: c.3020C>G
MANE Select: NM_000123
dbSNP: rs776583974
Type: single nucleotide variant
Location: chr13:102875362 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.91 · 10 PDB
Residue 1007: the 'interaction with pcna' region

Full ERCC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERCC5 p.Glu1090Lys Uncertain significance ★★ ⚠ same condition
ERCC5 p.Glu595Gln Uncertain significance ★★ ⚠ same condition
ERCC5 p.Ala376Val Likely benign ★★ same condition
ERCC5 p.Asp379= Likely benign ★★ same condition
ERCC5 p.Glu267= Benign/Likely benign ★★ same condition
ERCC5 p.Arg1166= Uncertain significance ★ same condition
ERCC5 p.Arg366Gln Uncertain significance ★ ⚠ same condition
ERCC5 p.Glu302Ala 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/ercc5-p-ala1007gly (accessed [today's date]).

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