Is ERCC1 p.Ser42Pro (c.124T>C) pathogenic?

ERCC1 p.Ser42Pro (c.124T>C) is classified Uncertain significance in ERCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-30). AlphaMissense: likely benign (0.0788); Absent from gnomAD v4.1.

How common is ERCC1 p.Ser42Pro (c.124T>C) in the general population?

ERCC1 p.Ser42Pro (c.124T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC1 p.Ser42Pro (c.124T>C)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

ERCC1 p.Ser42Pro

c.124T>C · rs772525358 · VCV1925023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.38	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 3.8	GERP 0.51, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.16 · regional, not allelic
Overall
CADD	18.4	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: ERCC1
Protein: p.Ser42Pro
Coding: c.124T>C
MANE Select: NM_001983
dbSNP: rs772525358
Type: single nucleotide variant
Location: chr19:45421375 (GRCh38)
Gene constraint: LOEUF 1.306 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 14 PDB

Full ERCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERCC1 p.Ser42Thr Uncertain significance ★ ⚠ same residue
ERCC1 c.526-1G>A Likely pathogenic ★★ same type
ERCC1 p.Arg41Ter Pathogenic ★★ same type
ERCC1 c.843+52A>G Uncertain significance ★★ same type
ERCC1 p.Ala265Thr Uncertain significance ★★ ⚠ same type
ERCC1 p.Arg156Gln Uncertain significance ★★ ⚠ same type
ERCC1 p.Arg207Trp Uncertain significance ★★ ⚠ same type
ERCC1 p.Asn110Ser Uncertain significance ★★ ⚠ 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/ercc1-p-ser42pro (accessed [today's date]).

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