Is ERCC8 p.Glu55fs (c.162del) pathogenic?

ERCC8 p.Glu55fs (c.162del) is classified Pathogenic/Likely pathogenic in ERCC8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-01). Very rare (popmax 0.000346%, nfe); Associated with Cockayne syndrome type 1.

What condition is associated with ERCC8 p.Glu55fs (c.162del)?

ERCC8 p.Glu55fs (c.162del) is associated with Cockayne syndrome type 1, UV-sensitive syndrome 2 (ClinVar).

How common is ERCC8 p.Glu55fs (c.162del) in the general population?

ERCC8 p.Glu55fs (c.162del) is very rare (popmax 0.000346%, nfe) (gnomAD).

How is Cockayne syndrome inherited?

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

ERCC8 p.Glu55fs

c.162del · rs756880941 · VCV1388419

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000346%, nfe)

Conditions

Cockayne syndrome type 1

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 6	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 0.000346% European (non-Finnish) · 4/1,155,488 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000349% 5/1,433,292 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00163%	61,436
European (non-Finnish)grpmax	0.000346%	288,872

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu55fs
Coding: c.162del
MANE Select: NM_000082
dbSNP: rs756880941
Type: Deletion
Location: chr5:60928875 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 16 PDB
Residue 55: a turn

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

Disease context

Cockayne syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: UV-sensitive syndrome 2

For Cockayne syndrome (Orphanet):

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

Similar variants

ERCC8 p.Arg217fs Pathogenic/Likely pathogenic ★★ same condition
ERCC8 p.Asn75fs Pathogenic ★★ same condition
ERCC8 p.Thr143fs Pathogenic/Likely pathogenic ★★ same condition
ERCC8 p.Trp127fs Pathogenic/Likely pathogenic ★★ same condition
ERCC8 p.Ala191del Likely pathogenic ★ same condition
ERCC8 p.Asn47fs Pathogenic ★ same condition
ERCC8 p.Asp199_Tyr200insTer Pathogenic ★ same condition
ERCC8 p.Asp227fs 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-glu55fs (accessed [today's date]).

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