ERCC3 p.Pro192=
c.576C>T · rs746534404 · VCV2176981
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
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. | ||
| REVEL | 0.199 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -5 |
| Overall | ||
| CADD | 0.987 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,888 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.0013%
21/1,613,936 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,722 |
| Admixed American | 0.005% | 19,998 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| East Asian | 0.00223% | 44,896 |
| European (non-Finnish) | 0.000932% | 107,270 |
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.Pro192=
- Coding
- c.576C>T
- MANE Select
- NM_000122
- dbSNP
- rs746534404
- Type
- single nucleotide variant
- Location
- chr2:127289770 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.34 · 56 PDB
- Residue 192
- 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-pro192 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown