Is ERCC6 p.Ala87fs (c.259_260del) pathogenic?

ERCC6 p.Ala87fs (c.259260del) is classified Likely pathogenic in ERCC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-05-12). Absent from gnomAD; Associated with de Sanctis-Cacchione syndrome.

What condition is associated with ERCC6 p.Ala87fs (c.259_260del)?

ERCC6 p.Ala87fs (c.259_260del) is associated with de Sanctis-Cacchione syndrome, cerebrooculofacioskeletal syndrome 1, Cockayne syndrome type 2 (ClinVar).

How common is ERCC6 p.Ala87fs (c.259_260del) in the general population?

ERCC6 p.Ala87fs (c.259_260del) is absent from gnomAD (gnomAD).

ERCC6 p.Ala87fs

c.259_260del · rs1554794620 · VCV551983

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

de Sanctis-Cacchione syndrome

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 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -3.9

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ERCC6
Protein: p.Ala87fs
Coding: c.259_260del
MANE Select: NM_000124
dbSNP: rs1554794620
Type: Microsatellite
Location: chr10:49532705 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 87: 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

de Sanctis-Cacchione syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cerebrooculofacioskeletal syndrome 1 Cockayne syndrome type 2

Similar variants

ERCC6 p.Asp366_Ser367insTer Pathogenic ★★ same condition
ERCC6 p.Cys573fs Pathogenic/Likely pathogenic ★★ same condition
ERCC6 p.Ser624fs Pathogenic ★★ same condition
ERCC6 p.Lys1198fs Pathogenic ★ same condition
ERCC6 p.Thr587fs Likely pathogenic ★ same condition
ERCC6 p.Arg1039del Uncertain significance ★ same condition
ERCC6 p.Glu382_Glu384del Uncertain significance ★ same condition
ERCC6 p.Glu43del Uncertain significance ★ 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-ala87fs (accessed [today's date]).

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