ERCC6 p.Ser1345=
c.4035A>G · rs2495946790 · VCV2840403
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.02 | GERP -3.6, phastCons 0.018 |
| Overall | ||
| CADD | 2.255 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,680 alleles
Overall
6.84e-05%
1/1,461,454 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
- ERCC6
- Protein
- p.Ser1345=
- Coding
- c.4035A>G
- MANE Select
- NM_000124
- dbSNP
- rs2495946790
- Type
- single nucleotide variant
- Location
- chr10:49460400 (GRCh38)
- Gene constraint
- LOEUF 0.803 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.12 · 12 PDB
- Residue 1345
- the 'disordered' region
Similar variants
- ERCC6 p.Ser1345Ter Pathogenic ★ same residue
- ERCC6 c.1397+1G>C Likely pathogenic ★★ same type
- ERCC6 c.1526+1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2169+1G>A Likely pathogenic ★★ same type
- ERCC6 c.2170-1G>A Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2286+1G>A Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2287-2A>G Pathogenic/Likely pathogenic ★★ same type
- ERCC6 c.2599-26A>G Pathogenic/Likely pathogenic ★★ same type
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/ercc6-p-ser1345 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown