XPC p.Thr683=
c.2049T>A · rs768068158 · VCV1142766
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.006 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -2.7 |
| Overall | ||
| CADD | 3.768 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,800 alleles
Filtering AF
0.00545%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.000868%
14/1,612,292 alleles · ultra-rare
exomes 13/1,460,110 · genomes 1/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,543 |
| East Asian | 0.00223% | 44,860 |
| South Asian | 0.0011% | 90,560 |
| European (non-Finnish) | 0.000424% | 235,850 |
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.Thr683=
- Coding
- c.2049T>A
- MANE Select
- NM_004628
- dbSNP
- rs768068158
- Type
- single nucleotide variant
- Location
- chr3:14152401 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.67 · 18 PDB
- Residue 683
- 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.Thr683fs 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
- XPC c.2420+2T>C Pathogenic/Likely pathogenic ★★ same type
- XPC c.299+1G>A 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-thr683 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown