XPC p.Asp575=
c.1725C>T · rs377666880 · VCV1161717
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, 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 -2.9 | GERP -3.4 |
| Overall | ||
| CADD | 2.154 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,864 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00905%
Overall
0.00198%
32/1,613,716 alleles · ultra-rare
exomes 24/1,461,712 · genomes 8/152,004 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,347 |
| Admixed American | 0.00333% | 29,991 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,232 |
| South Asian | 0.0022% | 45,536 |
| Finnishnot grpmax-eligible | 0.00156% | 63,998 |
| European (non-Finnish) | 0.000932% | 107,261 |
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.Asp575=
- Coding
- c.1725C>T
- MANE Select
- NM_004628
- dbSNP
- rs377666880
- Type
- single nucleotide variant
- Location
- chr3:14158158 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.67 · 18 PDB
- Residue 575
- the 'interaction with rad23b' 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-asp575 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown