XPC p.Ile899=
c.2697A>C · rs773031424 · VCV1152276
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, afr)
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 0.39 | GERP -2.1, phastCons 0.94 |
| Overall | ||
| CADD | 5.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,726 alleles
Filtering AF
0.00817%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00635%
Overall
0.000744%
12/1,612,646 alleles · ultra-rare
exomes 10/1,461,068 · genomes 2/151,578 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,793 |
| European (non-Finnish) | 8.48e-05% | 1,179,510 |
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.Ile899=
- Coding
- c.2697A>C
- MANE Select
- NM_004628
- dbSNP
- rs773031424
- Type
- single nucleotide variant
- Location
- chr3:14146067 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.67 · 18 PDB
- Residue 899
- the 'disordered' region; an α-helix; the 'interaction with ercc2 and gtf2h1' region
Similar variants
- 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
- XPC c.2420+2T>C Pathogenic/Likely pathogenic ★★ same type
- XPC c.299+1G>A Likely pathogenic ★★ same type
- XPC c.413-24A>G 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/xpc-p-ile899 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown