ERCC8 p.Ala135=
c.405A>G · rs2112495376 · VCV1077358
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 9.38e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor gain, 5 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.51 | GERP -2.9, phastCons 0.081 |
| Overall | ||
| CADD | 6.458 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.38e-05%
European (non-Finnish) · 1/1,066,038 alleles
Overall
7.48e-05%
1/1,336,948 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.Ala135=
- Coding
- c.405A>G
- MANE Select
- NM_000082
- dbSNP
- rs2112495376
- Type
- single nucleotide variant
- Location
- chr5:60904868 (GRCh38)
- Gene constraint
- LOEUF 1.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.72 · 16 PDB
- Residue 135
- a β-strand
Similar variants
- ERCC8 c.1041+1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.1042-2A>G Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.173+1119G>C Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.173+1G>A Pathogenic/Likely pathogenic ★★ same type
- ERCC8 c.275+1G>A Pathogenic ★★ same type
- ERCC8 c.276-1G>A Likely pathogenic ★★ same type
- ERCC8 c.399+1G>A Likely pathogenic ★★ same type
- ERCC8 c.551-1G>A 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/ercc8-p-ala135 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown