Is ERCC8 p.Arg218Ter (c.647_651dup) pathogenic?

ERCC8 p.Arg218Ter (c.647651dup) is classified Pathogenic in ERCC8 (ClinVar, Single submitter, 2 submitters; last evaluated 2017-03-21). Absent from gnomAD; Associated with Cockayne syndrome type 1.

What condition is associated with ERCC8 p.Arg218Ter (c.647_651dup)?

ERCC8 p.Arg218Ter (c.647_651dup) is associated with Cockayne syndrome type 1 (ClinVar).

How common is ERCC8 p.Arg218Ter (c.647_651dup) in the general population?

ERCC8 p.Arg218Ter (c.647_651dup) is absent from gnomAD (gnomAD).

How is Cockayne syndrome inherited?

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

ERCC8 p.Arg218Ter

c.647_651dup · rs1554073177 · VCV424544

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cockayne syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 1.5, phastCons 1

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: ERCC8
Protein: p.Arg218Ter
Coding: c.647_651dup
MANE Select: NM_000082
dbSNP: rs1554073177
Type: Duplication
Location: chr5:60899693 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 16 PDB

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

For Cockayne syndrome (Orphanet):

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

Similar variants

ERCC8 p.Cys157fs Pathogenic/Likely pathogenic ★★ same condition
ERCC8 p.Ile201fs Pathogenic ★★ same condition
ERCC8 p.Trp107Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC8 p.Arg92fs Likely pathogenic ★ same condition
ERCC8 p.Tyr366fs Uncertain significance same condition
ERCC8 c.1041+1G>T Pathogenic/Likely pathogenic ★★ same condition
ERCC8 c.1042-2A>G Pathogenic/Likely pathogenic ★★ same condition
ERCC8 c.173+1119G>C 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-arg218ter (accessed [today's date]).

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