Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele
Conditions
1
xeroderma pigmentosum group C
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 -4.3 | GERP -3.7 |
| Overall | ||
| CADD | 1.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
European (non-Finnish) · 1,179,880/1,179,880 alleles
Filtering AF
99.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 99.8%
Overall
100%
1,614,016/1,614,016 alleles · common
exomes 1,461,630/1,461,630 · genomes 152,386/152,386 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-American | 100% | 1 |
| Admixed American | 100% | 1 |
| East Asian | 100% | 1 |
| European (non-Finnish)grpmax | 100% | 1 |
| South Asian | 100% | 1 |
| Finnishnot grpmax-eligible | 100% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 100% | 1 |
| Amishnot grpmax-eligible | 100% | 1 |
| Middle Eastern | 100% | 1 |
| Remaining individualsnot grpmax-eligible | 100% | 1 |
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.Ala627=
- Coding
- c.1881T>A
- MANE Select
- NM_004628
- dbSNP
- rs2958057
- Type
- single nucleotide variant
- Location
- chr3:14156487 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.67 · 18 PDB
- Residue 627
- the 'interaction with rad23b' region; the 'minimal sensor domain involved in damage recognition' region; the 'dna-binding; preference for heteroduplex dna' region
Disease context
xeroderma pigmentosum group C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Xeroderma pigmentosum (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 1 000 000 (United States)
Similar variants
- XPC p.Ala627Val Uncertain significance ★ ⚠ same residue
- XPC c.104-2A>G Likely pathogenic ★★ same condition
- XPC c.1872+1G>A Likely pathogenic ★★ same condition
- XPC c.1872+1G>C Pathogenic/Likely pathogenic ★★ same condition
- XPC c.2033+1G>A Pathogenic/Likely pathogenic ★★ same condition
- XPC c.2251-1G>C Pathogenic ★★ same condition
- XPC c.2420+2T>C Pathogenic/Likely pathogenic ★★ same condition
- XPC c.299+1G>A Likely pathogenic ★★ same condition
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-ala627 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown