Is ERCC6 p.Ile263fs (c.787dup) pathogenic?

ERCC6 p.Ile263fs (c.787dup) is classified Likely pathogenic in ERCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). Associated with premature ovarian failure 11.

What condition is associated with ERCC6 p.Ile263fs (c.787dup)?

ERCC6 p.Ile263fs (c.787dup) is associated with premature ovarian failure 11, lung cancer, cerebrooculofacioskeletal syndrome 1 (ClinVar).

ERCC6 p.Ile263fs

c.787dup · VCV3595427

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

premature ovarian failure 11

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 5 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: ERCC6
Protein: p.Ile263fs
Coding: c.787dup
MANE Select: NM_000124
Type: Duplication
Location: chr10:49524642 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 263: the 'n-terminal domain; essential for its chromatin remodeling activity' region

Full ERCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

premature ovarian failure 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lung cancer cerebrooculofacioskeletal syndrome 1 de Sanctis-Cacchione syndrome UV-sensitive syndrome 1 age related macular degeneration 5 Cockayne syndrome type 2

Similar variants

ERCC6 p.Leu147fs Pathogenic ★★ same condition
ERCC6 p.Leu700fs Pathogenic/Likely pathogenic ★★ same condition
ERCC6 p.Pro70fs Pathogenic/Likely pathogenic ★★ same condition
ERCC6 p.Ser429fs Pathogenic ★★ same condition
ERCC6 p.Thr1138fs Pathogenic ★★ same condition
ERCC6 p.Thr659fs Pathogenic ★★ same condition
ERCC6 p.Thr699fs Pathogenic ★★ same condition
ERCC6 p.Arg261fs 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/ercc6-p-ile263fs (accessed [today's date]).

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