XPC p.Ala674=
c.2022G>A · rs200278513 · VCV732520
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, sas)
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 -2.8 | GERP -3.7 |
| Overall | ||
| CADD | 1.912 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
South Asian · 12/91,022 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00452%
73/1,613,494 alleles · ultra-rare
exomes 64/1,461,286 · genomes 9/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0132% | 7,585 |
| African / African-American | 0.00934% | 10,709 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
| European (non-Finnish) | 0.00415% | 24,076 |
| Admixed American | 0.00334% | 29,981 |
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
- XPC
- Protein
- p.Ala674=
- Coding
- c.2022G>A
- MANE Select
- NM_004628
- dbSNP
- rs200278513
- Type
- single nucleotide variant
- Location
- chr3:14156346 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.67 · 18 PDB
- Residue 674
- the 'interaction with rad23b' region; the 'minimal sensor domain involved in damage recognition' region; the 'dna-binding; preference for heteroduplex dna' region
Similar variants
- XPC p.Ala674Ser Uncertain significance ★ ⚠ same residue
- XPC p.Ala674Val Uncertain significance ★ same residue
- XPC p.Ala674fs Pathogenic/Likely pathogenic ★★ same residue
- XPC c.104-2A>G Likely pathogenic ★★ same type
- XPC c.1872+1G>A Likely pathogenic ★★ same type
- XPC c.1872+1G>C Pathogenic/Likely pathogenic ★★ same type
- XPC c.2033+1G>A Pathogenic/Likely pathogenic ★★ same type
- XPC c.2251-1G>C 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/xpc-p-ala674 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown