ERCC3 p.Ala41=
c.123G>A · rs761505994 · VCV3029188
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Conditions
1
ERCC3-related disorder
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 -2.9 | GERP -4.8 |
| Overall | ||
| CADD | 8.883 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,040 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000137%
2/1,461,872 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
- ERCC3
- Protein
- p.Ala41=
- Coding
- c.123G>A
- MANE Select
- NM_000122
- dbSNP
- rs761505994
- Type
- single nucleotide variant
- Location
- chr2:127293624 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.34 · 56 PDB
- Residue 41
- the 'disordered' region
Disease context
ERCC3-related disorder
Similar variants
- ERCC3 p.Ala41Val Uncertain significance ★ ⚠ same residue
- ERCC3 c.657+1G>A Likely pathogenic ★★ same condition
- ERCC3 p.Arg109Ter Pathogenic/Likely pathogenic ★★ same condition
- ERCC3 p.Gln154Ter Pathogenic/Likely pathogenic ★★ same condition
- ERCC3 p.Met1Ile Likely pathogenic ★ same condition
- ERCC3 p.Met1Thr Likely pathogenic ★ same condition
- ERCC3 p.Asp474fs Pathogenic/Likely pathogenic ★★ same condition
- ERCC3 p.Trp374Ter Pathogenic/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/ercc3-p-ala41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown