ERCC2 p.Arg143Gln
c.428G>A · rs150000483 · VCV1319432
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4425 | ambiguous |
|---|---|---|
| REVEL | 0.624 | indeterminate |
| SaProt | LLR -9.70 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 17 kb · p 0.48 · regional, not allelic |
| Overall | ||
| CADD | 25.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.155% | 644 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,165 |
| East Asiangrpmax | 0.0111% | 8,979 |
| South Asian | 0.0022% | 45,540 |
| European (non-Finnish) | 0.00203% | 49,167 |
| African / African-American | 0.00133% | 74,936 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg143Gln
- Coding
- c.428G>A
- MANE Select
- NM_000400
- dbSNP
- rs150000483
- Type
- single nucleotide variant
- Location
- chr19:45365091 (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 143
- the helicase atp-binding domain; an α-helix
Disease context
xeroderma pigmentosum — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Xeroderma pigmentosum (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 1 000 000 (United States)
Similar variants
- ERCC2 p.Arg143Trp Uncertain significance ★★ ⚠ same residue
- ERCC2 p.Arg143= Likely benign ★ same residue
- ERCC2 c.816-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Ala717Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg511Gln Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg601Leu Pathogenic/Likely pathogenic ★★ same condition
- ERCC2 p.Arg616Pro Pathogenic ★★ 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-arg143gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown