ERCC2 p.Arg282=
c.846G>A · rs527681176 · VCV1097102
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.072%, eas)
Conditions
1
Inborn genetic diseases
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 -0.81 | GERP -3.4, phastCons 0.003 |
| Overall | ||
| CADD | 6.313 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.072%
East Asian · 32/44,420 alleles
Filtering AF
0.0524%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0457%
Overall
0.0048%
77/1,603,776 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.072% | 1,388 |
| European (non-Finnish) | 0.00374% | 26,723 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,026 |
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.Arg282=
- Coding
- c.846G>A
- MANE Select
- NM_000400
- dbSNP
- rs527681176
- Type
- single nucleotide variant
- Location
- chr19:45364089 (GRCh38)
- Gene constraint
- LOEUF 1.089 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.74 · 55 PDB
- Residue 282
- the helicase atp-binding domain; an α-helix
Similar variants
- ERCC2 p.Arg282Gln Uncertain significance ★ ⚠ same residue
- ERCC2 p.Arg282Leu Uncertain significance ★ ⚠ same residue
- ERCC2 p.Arg282Pro Uncertain significance ★ ⚠ same residue
- ERCC2 p.Arg282Trp Uncertain significance ★ ⚠ same residue
- ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg616Pro Pathogenic ★★ same condition
- ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala144Val Uncertain significance ★★ ⚠ same condition
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-arg282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown