Is ERCC4 p.Ala808Val (c.2423C>T) pathogenic?

ERCC4 p.Ala808Val (c.2423C>T) is classified Uncertain significance in ERCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-15). AlphaMissense: likely benign (0.0953); Absent from gnomAD v4.1; Associated with xeroderma pigmentosum group F.

What condition is associated with ERCC4 p.Ala808Val (c.2423C>T)?

ERCC4 p.Ala808Val (c.2423C>T) is associated with xeroderma pigmentosum group F, Fanconi anemia complementation group Q, Cockayne syndrome (ClinVar).

How common is ERCC4 p.Ala808Val (c.2423C>T) in the general population?

ERCC4 p.Ala808Val (c.2423C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC4 p.Ala808Val (c.2423C>T)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

ERCC4 p.Ala808Val

Q: How is Xeroderma pigmentosum-Cockayne syndrome complex inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2423C>T · VCV3763282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xeroderma pigmentosum group F

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -10.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 28 kb · p 0.011 · regional, not allelic
Overall
CADD	18.44	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: ERCC4
Protein: p.Ala808Val
Coding: c.2423C>T
MANE Select: NM_005236
Type: single nucleotide variant
Location: chr16:13948019 (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 808: the 'nuclease' region

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

Disease context

xeroderma pigmentosum group F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group Q Cockayne syndrome

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ERCC4 p.Ala808Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ERCC4 p.Ala808= Likely benign ★ same residue
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

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-ala808val (accessed [today's date]).

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