Is ERCC8 p.Asp37fs (c.109_110del) pathogenic?

ERCC8 p.Asp37fs (c.109110del) is classified Pathogenic in ERCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-18). Very rare (popmax 0.00267%, afr); Associated with Cockayne syndrome.

What condition is associated with ERCC8 p.Asp37fs (c.109_110del)?

ERCC8 p.Asp37fs (c.109_110del) is associated with Cockayne syndrome (ClinVar).

How common is ERCC8 p.Asp37fs (c.109_110del) in the general population?

ERCC8 p.Asp37fs (c.109_110del) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Cockayne syndrome inherited?

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

ERCC8 p.Asp37fs

c.109_110del · VCV4536127

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Cockayne 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 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000206% 3/1,455,824 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
European (non-Finnish)	8.51e-05%	1,175,630

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERCC8
Protein: p.Asp37fs
Coding: c.109_110del
MANE Select: NM_000082
Type: Microsatellite
Location: chr5:60928927 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 16 PDB
Residue 37: a β-strand

Full ERCC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cockayne syndrome — 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

ERCC8 p.Asp37Asn Uncertain significance ★ ⚠ same residue
ERCC8 p.Asp37= Likely benign ★ same residue
ERCC8 c.275+1G>A Pathogenic ★★ same condition
ERCC8 c.399+1G>A Likely pathogenic ★★ same condition
ERCC8 p.Ala160Thr Likely pathogenic ★★ same condition
ERCC8 p.Ala160Val Pathogenic/Likely pathogenic ★★ same condition
ERCC8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC8 p.Glu13Ter 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/ercc8-p-asp37fs (accessed [today's date]).

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