Is XPC p.Ile832= (c.2496T>C) pathogenic?

XPC p.Ile832= (c.2496T>C) is classified Conflicting classifications of pathogenicity in XPC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.12%, nfe); Associated with xeroderma pigmentosum.

What condition is associated with XPC p.Ile832= (c.2496T>C)?

XPC p.Ile832= (c.2496T>C) is associated with xeroderma pigmentosum, xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Ile832= (c.2496T>C) in the general population?

XPC p.Ile832= (c.2496T>C) is rare (popmax 0.12%, nfe) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

XPC p.Ile832=

c.2496T>C · rs201597537 · VCV712680

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.12%, nfe)

Conditions

xeroderma pigmentosum

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.1	GERP -3.1
Overall
CADD	0.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% European (non-Finnish) · 1,408/1,174,028 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.0987% 1,582/1,602,478 alleles · rare exomes 1,455/1,450,244 · genomes 127/152,234 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.127%	790
European (non-Finnish)grpmax	0.12%	834
Remaining individualsnot grpmax-eligible	0.0693%	1,443
Admixed American	0.041%	2,438
Ashkenazi Jewishnot grpmax-eligible	0.0375%	2,667
African / African-American	0.0214%	4,683

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile832=
Coding: c.2496T>C
MANE Select: NM_004628
dbSNP: rs201597537
Type: single nucleotide variant
Location: chr3:14147926 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 832: the 'interaction with ercc2 and gtf2h1' region

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

Disease context

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

Also linked: xeroderma pigmentosum group C

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-ile832 (accessed [today's date]).

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