ERCC2 p.Arg373=
c.1117A>C · rs766208120 · VCV2146620
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.124%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.26 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.2 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 19.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.124%
Admixed American · 63/50,944 alleles
Filtering AF
0.0992%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0902%
Overall
0.00418%
64/1,532,416 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.124% | 809 |
| Remaining individualsnot grpmax-eligible | 0.00168% | 59,698 |
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
- ERCC2
- Protein
- p.Arg373=
- Coding
- c.1117A>C
- MANE Select
- NM_000400
- dbSNP
- rs766208120
- Type
- single nucleotide variant
- Location
- chr19:45363744 (GRCh38)
- Gene constraint
- LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.74 · 55 PDB
Similar variants
- ERCC2 p.Arg373Gly Uncertain significance ★ ⚠ same residue
- MAG p.Ser373= Likely benign ★ same residue
- ERCC2 c.1238-1G>C Likely pathogenic ★★ same type
- ERCC2 c.1308-2A>G Likely pathogenic ★★ same type
- ERCC2 c.1378-1G>T Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1479+2T>C Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1480-1G>C Pathogenic/Likely pathogenic ★★ same type
- ERCC2 c.1480-2A>C 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/ercc2-p-arg373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown