ERCC3 p.Ala724=
c.2172C>T · rs778824043 · VCV720761
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
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 -3.6 | GERP -4.2 |
| Overall | ||
| CADD | 1.963 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,880 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000744%
12/1,613,942 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,720 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| South Asian | 0.0022% | 45,538 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| Finnishnot grpmax-eligible | 0.00156% | 64,018 |
| European (non-Finnish) | 0.000254% | 393,342 |
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.Ala724=
- Coding
- c.2172C>T
- MANE Select
- NM_000122
- dbSNP
- rs778824043
- Type
- single nucleotide variant
- Location
- chr2:127259341 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.34 · 56 PDB
- Residue 724
- an α-helix
Similar variants
- 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
- ERCC3 p.Arg452Ter 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/ercc3-p-ala724 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown