XPC p.Asp622=
c.1866C>T · rs780075155 · VCV766765
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.106%, eas)
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 0.5 | GERP -2.6, phastCons 0.032 |
| Overall | ||
| CADD | 3.106 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.106%
East Asian · 47/44,462 alleles
Filtering AF
0.0816%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0731%
Overall
0.00326%
52/1,597,382 alleles · rare
exomes 42/1,445,052 · genomes 10/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.106% | 946 |
| Remaining individualsnot grpmax-eligible | 0.00811% | 12,326 |
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.Asp622=
- Coding
- c.1866C>T
- MANE Select
- NM_004628
- dbSNP
- rs780075155
- Type
- single nucleotide variant
- Location
- chr3:14158017 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.67 · 18 PDB
- Residue 622
- 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 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-asp622 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown