Is ERCC6 p.Asp385fs (c.1154delinsTACACTTTT) pathogenic?

ERCC6 p.Asp385fs (c.1154delinsTACACTTTT) is classified Likely pathogenic in ERCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-14). Absent from gnomAD; Associated with Cockayne syndrome type 2.

What condition is associated with ERCC6 p.Asp385fs (c.1154delinsTACACTTTT)?

ERCC6 p.Asp385fs (c.1154delinsTACACTTTT) is associated with Cockayne syndrome type 2 (ClinVar).

How common is ERCC6 p.Asp385fs (c.1154delinsTACACTTTT) in the general population?

ERCC6 p.Asp385fs (c.1154delinsTACACTTTT) is absent from gnomAD (gnomAD).

How is Cockayne syndrome inherited?

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

ERCC6 p.Asp385fs

c.1154delinsTACACTTTT · rs2496139138 · VCV1725200

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cockayne syndrome type 2

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 -1.8	GERP 0.12
Region caveats
Repeat context	tandem	(TCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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.Asp385fs
Coding: c.1154delinsTACACTTTT
MANE Select: NM_000124
dbSNP: rs2496139138
Type: Indel
Location: chr10:49524276 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.12 · 12 PDB
Residue 385: the 'disordered' region; 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

Cockayne syndrome type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cockayne syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ERCC6 p.Asp385His Uncertain significance ★★ ⚠ same residue
ERCC6 p.Leu1001fs Likely pathogenic ★ same condition
ERCC6 p.Lys1258fs Likely pathogenic ★ same condition
ERCC6 p.Thr623fs Likely pathogenic ★ same condition
ERCC6 p.Asp385Asn Uncertain significance ★ ⚠ same residue
ERCC6 p.Glu608fs Likely pathogenic same condition
ERCC6 c.1397+1G>C Likely pathogenic ★★ same condition
ERCC6 c.1526+1G>T 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/ercc6-p-asp385fs (accessed [today's date]).

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