ERCC2 p.Ala680=
c.2040C>T · rs374379149 · VCV1129927
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Conditions
1
Inborn genetic diseases
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 -20 | GERP -2.5 |
| Overall | ||
| CADD | 0.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00702%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00652%
Overall
0.00774%
125/1,614,144 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,814 |
| East Asian | 0.00891% | 11,220 |
| European (non-Finnish) | 0.00839% | 11,919 |
| Admixed American | 0.00833% | 12,006 |
| South Asian | 0.00659% | 15,179 |
| Finnishnot grpmax-eligible | 0.00156% | 63,998 |
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.Ala680=
- Coding
- c.2040C>T
- MANE Select
- NM_000400
- dbSNP
- rs374379149
- Type
- single nucleotide variant
- Location
- chr19:45352512 (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 680
- a β-strand
Similar variants
- ERCC2 p.Ala680Thr Uncertain significance ★ ⚠ same residue
- ERCC2 p.Ala680Val Uncertain significance ★ ⚠ same residue
- ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg616Pro Pathogenic ★★ same condition
- ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala144Val Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala226Thr Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala306Val Uncertain significance ★★ ⚠ 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/ercc2-p-ala680 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown