Is ERCC3 p.Asp81fs (c.240dup) pathogenic?

ERCC3 p.Asp81fs (c.240dup) is classified Likely pathogenic in ERCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-08). Associated with xeroderma pigmentosum group B.

What condition is associated with ERCC3 p.Asp81fs (c.240dup)?

ERCC3 p.Asp81fs (c.240dup) is associated with xeroderma pigmentosum group B (ClinVar).

ERCC3 p.Asp81fs

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

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

c.240dup · VCV3779625

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

xeroderma pigmentosum group B

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 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1

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

Variant & gene context

Gene: ERCC3
Protein: p.Asp81fs
Coding: c.240dup
MANE Select: NM_000122
Type: Duplication
Location: chr2:127292840 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.34 · 56 PDB

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

Disease context

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

For Xeroderma pigmentosum-Cockayne syndrome complex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ERCC3 p.Asp474fs Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Trp374Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC3 p.Asp81Asn Uncertain significance ★ ⚠ same residue
ERCC3 p.Glu588fs Conflicting classifications of pathogenicity ★ same condition
ERCC3 c.1828-1G>C Likely pathogenic ★★ same condition
ERCC3 c.471+1G>A Pathogenic ★★ same condition
ERCC3 c.657+1G>A Likely pathogenic ★★ same condition
ERCC3 p.Arg109Ter 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-asp81fs (accessed [today's date]).

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