Is ERCC5 p.Ser341Thr (c.1021T>A) pathogenic?

ERCC5 p.Ser341Thr (c.1021T>A) is classified Uncertain significance in ERCC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-07). AlphaMissense: likely benign (0.1463); Absent from gnomAD v4.1; Associated with cerebrooculofacioskeletal syndrome 3.

What condition is associated with ERCC5 p.Ser341Thr (c.1021T>A)?

ERCC5 p.Ser341Thr (c.1021T>A) is associated with cerebrooculofacioskeletal syndrome 3, xeroderma pigmentosum group G (ClinVar).

How common is ERCC5 p.Ser341Thr (c.1021T>A) in the general population?

ERCC5 p.Ser341Thr (c.1021T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC5 p.Ser341Thr (c.1021T>A)?

AlphaMissense predicts likely benign (score 0.1463) — an in-silico prediction, not a clinical call.

ERCC5 p.Ser341Thr

c.1021T>A · VCV3575650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1463 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cerebrooculofacioskeletal syndrome 3

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1463	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.1	GERP 0.75, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 22 kb · p 0.087 · regional, not allelic
Overall
CADD	22.9	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.Ser341Thr
Coding: c.1021T>A
MANE Select: NM_000123
Type: single nucleotide variant
Location: chr13:102862170 (GRCh38)

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

Disease context

cerebrooculofacioskeletal syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group G

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-ser341thr (accessed [today's date]).

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