Is ERCC4 p.Pro272= (c.816T>A) pathogenic?

ERCC4 p.Pro272= (c.816T>A) is classified Likely benign in ERCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-10). Absent from gnomAD v4.1; Associated with Fanconi anemia complementation group Q.

What condition is associated with ERCC4 p.Pro272= (c.816T>A)?

ERCC4 p.Pro272= (c.816T>A) is associated with Fanconi anemia complementation group Q, xeroderma pigmentosum group F, Cockayne syndrome (ClinVar).

How common is ERCC4 p.Pro272= (c.816T>A) in the general population?

ERCC4 p.Pro272= (c.816T>A) is absent from gnomAD v4.1 (gnomAD).

ERCC4 p.Pro272=

c.816T>A · rs2141948404 · VCV1107043

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Fanconi anemia complementation group Q

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.38, phastCons 1
Overall
CADD	14.27	PHRED · no single calibrated threshold — expert panels disagree

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: ERCC4
Protein: p.Pro272=
Coding: c.816T>A
MANE Select: NM_005236
dbSNP: rs2141948404
Type: single nucleotide variant
Location: chr16:13930733 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 13 PDB
Residue 272: the 'helicase-like' region; the 'leucine-zipper 2' region

Full ERCC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fanconi anemia complementation group Q — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group F Cockayne syndrome

Similar variants

ERCC4 c.1102+1G>T Likely pathogenic ★★ same condition
ERCC4 c.793-2A>G Pathogenic ★★ same condition
ERCC4 p.Arg20Ter Pathogenic ★★ same condition
ERCC4 p.Arg589Trp Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Arg689Ser Likely pathogenic ★★ same condition
ERCC4 p.Arg772Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Cys236Arg Pathogenic/Likely pathogenic ★★ same condition
ERCC4 p.Cys723Ter 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/ercc4-p-pro272 (accessed [today's date]).

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