Is XPC p.Val696= (c.2088G>A) pathogenic?

XPC p.Val696= (c.2088G>A) is classified Conflicting classifications of pathogenicity in XPC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-18). Rare (popmax 0.148%, afr); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Val696= (c.2088G>A)?

XPC p.Val696= (c.2088G>A) is associated with xeroderma pigmentosum group C, xeroderma pigmentosum (ClinVar).

How common is XPC p.Val696= (c.2088G>A) in the general population?

XPC p.Val696= (c.2088G>A) is rare (popmax 0.148%, afr) (gnomAD).

How is Xeroderma pigmentosum inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

XPC p.Val696=

c.2088G>A · rs182189497 · VCV695560

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, afr)

Conditions

xeroderma pigmentosum group C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.165	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.09	GERP 0.56, phastCons 0.91
Overall
CADD	7.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% African / African-American · 111/75,028 alleles

Filtering AF 0.126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.117%

Overall 0.00769% 124/1,613,400 alleles · rare exomes 63/1,461,102 · genomes 61/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.148%	676
Remaining individualsnot grpmax-eligible	0.0112%	8,923
South Asian	0.0044%	22,716
Admixed American	0.00167%	59,964
European (non-Finnish)	8.48e-05%	1,179,677

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.Val696=
Coding: c.2088G>A
MANE Select: NM_004628
dbSNP: rs182189497
Type: single nucleotide variant
Location: chr3:14152362 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 696: the 'interaction with rad23b' region; the 'minimal sensor domain involved in damage recognition' region; the 'dna-binding; preference for heteroduplex dna' region

Full XPC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

xeroderma pigmentosum group C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum

For Xeroderma pigmentosum (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

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
XPC c.413-24A>G Pathogenic/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-val696 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown