Is ERCC8 p.Gln347= (c.1041G>A) pathogenic?

ERCC8 p.Gln347= (c.1041G>A) is classified Pathogenic in ERCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-24). Very rare (popmax 0.000425%, nfe); Associated with Cockayne syndrome type 1.

What condition is associated with ERCC8 p.Gln347= (c.1041G>A)?

ERCC8 p.Gln347= (c.1041G>A) is associated with Cockayne syndrome type 1 (ClinVar).

How common is ERCC8 p.Gln347= (c.1041G>A) in the general population?

ERCC8 p.Gln347= (c.1041G>A) is very rare (popmax 0.000425%, nfe) (gnomAD).

How is Cockayne syndrome inherited?

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

ERCC8 p.Gln347=

c.1041G>A · VCV3338104

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Conditions

Cockayne syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.91	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.60	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000425% European (non-Finnish) · 5/1,177,306 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000343% 5/1,458,460 alleles · very rare

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.Gln347=
Coding: c.1041G>A
MANE Select: NM_000082
Type: single nucleotide variant
Location: chr5:60890889 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 16 PDB
Residue 347: a UniProt-annotated variant site (in csa); 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

For Cockayne syndrome (Orphanet):

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

Similar variants

ERCC8 p.Gln347Arg Uncertain significance ★ same residue
ERCC8 p.Gln347His Uncertain significance ★ ⚠ 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

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-gln347 (accessed [today's date]).

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