Is ERCC1 p.Val10fs (c.23dup) pathogenic?

ERCC1 p.Val10fs (c.23dup) is classified Likely pathogenic in ERCC1 (ClinVar, Single submitter, 1 submitter). Associated with cerebrooculofacioskeletal syndrome 4.

What condition is associated with ERCC1 p.Val10fs (c.23dup)?

ERCC1 p.Val10fs (c.23dup) is associated with cerebrooculofacioskeletal syndrome 4 (ClinVar).

ERCC1 p.Val10fs

c.23dup · VCV3391184

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

cerebrooculofacioskeletal syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.23	GERP -3.6, phastCons 0.011

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ERCC1
Protein: p.Val10fs
Coding: c.23dup
MANE Select: NM_001983
Type: Duplication
Location: chr19:45423351 (GRCh38)
Gene constraint: LOEUF 1.306 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 14 PDB
Residue 10: the 'disordered' region

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

Disease context

cerebrooculofacioskeletal syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERCC1 p.Arg41Ter Pathogenic ★★ same condition
ERCC1 p.Arg156Gln Uncertain significance ★★ ⚠ same condition
ERCC1 p.Asn110Ser Uncertain significance ★★ ⚠ same condition
ERCC1 p.Ser267Pro Uncertain significance ★★ ⚠ same condition
ERCC1 c.843+32G>A Benign/Likely benign ★★ same condition
POLR1G p.Thr282Ala Benign ★★ same condition
ERCC1 p.Glu62Ter Likely pathogenic ★ same condition
ERCC1 p.Phe231Leu 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/ercc1-p-val10fs (accessed [today's date]).

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