Is ERCC3 p.Thr119Pro (c.355A>C) pathogenic?

ERCC3 p.Thr119Pro (c.355A>C) is classified Pathogenic in ERCC3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1997-02-01). AlphaMissense: likely pathogenic (0.9671); Absent from gnomAD v4.1; Associated with trichothiodystrophy 2, photosensitive.

What condition is associated with ERCC3 p.Thr119Pro (c.355A>C)?

ERCC3 p.Thr119Pro (c.355A>C) is associated with trichothiodystrophy 2, photosensitive (ClinVar).

How common is ERCC3 p.Thr119Pro (c.355A>C) in the general population?

ERCC3 p.Thr119Pro (c.355A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC3 p.Thr119Pro (c.355A>C)?

AlphaMissense predicts likely pathogenic (score 0.9671) — an in-silico prediction, not a clinical call.

ERCC3 p.Thr119Pro

c.355A>C · rs121913046 · VCV16584

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

trichothiodystrophy 2, photosensitive

Computational evidence

Protein change
AlphaMissense	0.9671	likely pathogenic ✓ concordant with ClinVar
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -12.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.71	acceptor loss, 22 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 36 kb · p 4.8e-07 · regional, not allelic
Overall
CADD	32.0	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.Thr119Pro
Coding: c.355A>C
MANE Select: NM_000122
dbSNP: rs121913046
Type: single nucleotide variant
Location: chr2:127292726 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB
Residue 119: a UniProt-annotated variant site (in ttd2; mild; wild-type dual incision, opening around damaged dna and transcription by tfiih)

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

Disease context

trichothiodystrophy 2, photosensitive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERCC3 c.1828-1G>C Likely pathogenic ★★ same condition
ERCC3 c.657+1G>A Likely pathogenic ★★ same condition
ERCC3 p.Arg109Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Arg425Ter Pathogenic ★★ same condition
ERCC3 p.Arg452Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Arg530Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Arg574Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Gln388Ter Pathogenic/Likely pathogenic ★★ 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-thr119pro (accessed [today's date]).

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