ERCC1 p.Pro128=
c.384C>T · rs139827427 · VCV709100
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0503%, nfe)
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 -3.3 |
| Overall | ||
| CADD | 0.103 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0503%
European (non-Finnish) · 594/1,179,842 alleles
Filtering AF
0.047%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0456%
Overall
0.0408%
659/1,613,746 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0503% | 1,986 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,677 |
| South Asian | 0.0209% | 4,788 |
| African / African-American | 0.02% | 5,001 |
| Admixed American | 0.015% | 6,665 |
| Finnishnot grpmax-eligible | 0.00312% | 32,002 |
| East Asian | 0.00223% | 44,858 |
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
- ERCC1
- Protein
- p.Pro128=
- Coding
- c.384C>T
- MANE Select
- NM_001983
- dbSNP
- rs139827427
- Type
- single nucleotide variant
- Location
- chr19:45420365 (GRCh38)
- Gene constraint
- LOEUF 1.306 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.48 · 14 PDB
- Residue 128
- a β-strand
Similar variants
- ERCC1 c.526-1G>A Likely pathogenic ★★ same type
- ERCC1 p.Arg41Ter Pathogenic ★★ same type
- ERCC1 c.843+52A>G Uncertain significance ★★ same type
- ERCC1 p.Ala265Thr Uncertain significance ★★ ⚠ same type
- ERCC1 p.Arg156Gln Uncertain significance ★★ ⚠ same type
- ERCC1 p.Arg207Trp Uncertain significance ★★ same type
- ERCC1 p.Asn110Ser Uncertain significance ★★ ⚠ same type
- ERCC1 p.Gly85Arg Uncertain significance ★★ ⚠ 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/ercc1-p-pro128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown