ERCC3 p.Ala219=
c.657C>T · rs771683698 · VCV1008945
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.148%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.022 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -5 |
| Overall | ||
| CADD | 2.297 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.148%
Middle Eastern · 9/6,070 alleles
Filtering AF
0.0773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0578%
Overall
0.00198%
32/1,613,920 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.148% | 674 |
| Admixed American | 0.0133% | 7,499 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| African / African-American | 0.00401% | 24,962 |
| European (non-Finnish) | 0.000763% | 131,111 |
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.Ala219=
- Coding
- c.657C>T
- MANE Select
- NM_000122
- dbSNP
- rs771683698
- Type
- single nucleotide variant
- Location
- chr2:127289689 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.34 · 56 PDB
- Residue 219
- the 'disordered' region
Similar variants
- ERCC3 p.Ala219Thr Uncertain significance ★ ⚠ same residue
- ERCC3 c.1828-1G>C Likely pathogenic ★★ same type
- ERCC3 c.471+1G>A Pathogenic ★★ same type
- ERCC3 c.657+1G>A Likely pathogenic ★★ same type
- ERCC3 p.Arg109Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC3 p.Arg195Ter Pathogenic ★★ same type
- ERCC3 p.Arg234Ter Pathogenic/Likely pathogenic ★★ same type
- ERCC3 p.Arg425Ter 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/ercc3-p-ala219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown