ERCC2 p.Val340=
c.1020G>A · rs1167976357 · VCV2808054
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0019%, amr)
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 1.8 | GERP -0.51, phastCons 1 |
| Overall | ||
| CADD | 9.926 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0019%
Admixed American · 1/52,670 alleles
Overall
7.16e-05%
1/1,395,948 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
- ERCC2
- Protein
- p.Val340=
- Coding
- c.1020G>A
- MANE Select
- NM_000400
- dbSNP
- rs1167976357
- Type
- single nucleotide variant
- Location
- chr19:45363841 (GRCh38)
- Gene constraint
- LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.74 · 55 PDB
- Residue 340
- an α-helix
Similar variants
- ERCC2 p.Val340Leu Uncertain significance ★★ ⚠ same residue
- ERCC2 p.Val340Met Uncertain significance ★ ⚠ same residue
- ERCC2 p.Val340fs Pathogenic ★ same residue
- ERCC2 c.1238-1G>C Likely pathogenic ★★ same type
- ERCC2 c.1308-2A>G Likely pathogenic ★★ same type
- ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1479+2T>C Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1480-1G>C 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/ercc2-p-val340 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown