ERCC2 p.Arg683=
c.2049G>A · rs1971834921 · VCV2989029
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 -1.3 | GERP -3.1 |
| Overall | ||
| CADD | 0.607 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,028 alleles
Overall
6.84e-05%
1/1,461,698 alleles · very rare
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.Arg683=
- Coding
- c.2049G>A
- MANE Select
- NM_000400
- dbSNP
- rs1971834921
- Type
- single nucleotide variant
- Location
- chr19:45352350 (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 683
- an α-helix; a UniProt-annotated variant site (in xp-d); a UniProt-annotated variant site (in xp-d; vitamin d-mediated activation of cyp24a1 is impaired in patient fibroblasts due to altered tfiih-dependent phosphorylation of ets1, subsequent impaired cooperation of ets1 with vdr and altered vdr recruitment to cyp24a1 promoter; damaged dna opening by tfiih is impeded)
Similar variants
- ERCC2 p.Arg683Gln Pathogenic ★★ same residue
- ERCC2 p.Arg683Trp Pathogenic/Likely pathogenic ★★ 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
- ERCC2 p.Ala226Thr Uncertain significance ★★ ⚠ same condition
- ERCC2 p.Ala306Val 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-arg683 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown