Is XPC p.Arg100= (c.300G>A) pathogenic?

XPC p.Arg100= (c.300G>A) is classified Benign in XPC (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 7.86%, afr) — too common for a highly-penetrant pathogenic allele; Associated with xeroderma pigmentosum group A.

What condition is associated with XPC p.Arg100= (c.300G>A)?

XPC p.Arg100= (c.300G>A) is associated with xeroderma pigmentosum group A, xeroderma pigmentosum group C (ClinVar).

How is Xeroderma pigmentosum inherited?

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

XPC p.Arg100=

Q: How common is XPC p.Arg100= (c.300G>A) in the general population?

XPC p.Arg100= (c.300G>A) is common (popmax 7.86%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.300G>A · rs2228002 · VCV135476

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 7.86%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

xeroderma pigmentosum group A

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 -0.2	GERP -1.7
Overall
CADD	11.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.86% African / African-American · 5,881/74,804 alleles

Filtering AF 7.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.63%

Overall 0.414% 6,657/1,608,880 alleles · common exomes 3,317/1,456,642 · genomes 3,340/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.86%	13
Admixed American	0.533%	188
Remaining individualsnot grpmax-eligible	0.495%	202
Middle Eastern	0.149%	671
South Asian	0.0122%	8,210
European (non-Finnish)	0.011%	9,124
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,460
East Asian	0.00223%	44,752

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.Arg100=
Coding: c.300G>A
MANE Select: NM_004628
dbSNP: rs2228002
Type: single nucleotide variant
Location: chr3:14170550 (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 A — 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-arg100 (accessed [today's date]).

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