Is XPC p.Asp101= (c.303C>T) pathogenic?

XPC p.Asp101= (c.303C>T) is classified Benign in XPC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.81%, sas); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Asp101= (c.303C>T)?

XPC p.Asp101= (c.303C>T) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Asp101= (c.303C>T) in the general population?

XPC p.Asp101= (c.303C>T) is low-frequency (popmax 1.81%, sas) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

XPC p.Asp101=

c.303C>T · rs41545713 · VCV695695

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.81%, sas)

Conditions

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 2.1	GERP -0.73, phastCons 0.42
Overall
CADD	4.778	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.81% South Asian · 1,639/90,492 alleles

Filtering AF 1.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.71%

Overall 0.211% 3,406/1,610,506 alleles · low-frequency exomes 3,188/1,458,188 · genomes 218/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.81%	55
Middle Eastern	0.958%	104
Remaining individualsnot grpmax-eligible	0.239%	419
European (non-Finnish)	0.125%	800
Admixed American	0.0922%	1,085
Ashkenazi Jewishnot grpmax-eligible	0.0407%	2,459
African / African-American	0.02%	4,995
Finnishnot grpmax-eligible	0.00469%	21,315
East Asian	0.00447%	22,390

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.Asp101=
Coding: c.303C>T
MANE Select: NM_004628
dbSNP: rs41545713
Type: single nucleotide variant
Location: chr3:14170547 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB

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

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-asp101 (accessed [today's date]).

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