Is ERCC8 p.Ser61Ter (c.182C>G) pathogenic?

ERCC8 p.Ser61Ter (c.182C>G) is classified Pathogenic/Likely pathogenic in ERCC8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-06-03). Absent from gnomAD v4.1; Associated with UV-sensitive syndrome 2.

What condition is associated with ERCC8 p.Ser61Ter (c.182C>G)?

ERCC8 p.Ser61Ter (c.182C>G) is associated with UV-sensitive syndrome 2, Cockayne syndrome type 1 (ClinVar).

How common is ERCC8 p.Ser61Ter (c.182C>G) in the general population?

ERCC8 p.Ser61Ter (c.182C>G) is absent from gnomAD v4.1 (gnomAD).

How is UV-sensitive syndrome inherited?

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

ERCC8 p.Ser61Ter

c.182C>G · rs1749618632 · VCV984264

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

UV-sensitive syndrome 2

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 3 of 12
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERCC8
Protein: p.Ser61Ter
Coding: c.182C>G
MANE Select: NM_000082
dbSNP: rs1749618632
Type: single nucleotide variant
Location: chr5:60922147 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 16 PDB
Residue 61: a β-strand

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

Disease context

UV-sensitive syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cockayne syndrome type 1

For UV-sensitive syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

ERCC8 p.Ser61= Likely benign ★ same residue
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
ERCC8 c.173+1G>A Pathogenic/Likely pathogenic ★★ same condition
ERCC8 c.275+1G>A Pathogenic ★★ same condition
ERCC8 c.276-1G>A Likely pathogenic ★★ same condition
ERCC8 c.399+1G>A 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-ser61ter (accessed [today's date]).

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