Is XPC p.Arg687= (c.2061G>A) pathogenic?

XPC p.Arg687= (c.2061G>A) is classified Benign/Likely benign in XPC (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 30.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with xeroderma pigmentosum group A.

What condition is associated with XPC p.Arg687= (c.2061G>A)?

XPC p.Arg687= (c.2061G>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.Arg687=

Q: How common is XPC p.Arg687= (c.2061G>A) in the general population?

XPC p.Arg687= (c.2061G>A) is common (popmax 30.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2061G>A · rs2227998 · VCV135469

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 30.5%, 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.
REVEL	0.058	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.6, phastCons 0.99
Overall
CADD	12.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.5% African / African-American · 22,810/74,894 alleles

Filtering AF 30.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 30%

Overall 26.1% 420,984/1,611,184 alleles · common exomes 381,438/1,459,068 · genomes 39,546/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.5%	3
Admixed American	29.7%	3
South Asian	28.6%	3
European (non-Finnish)	26.7%	4
Remaining individualsnot grpmax-eligible	25.1%	4
Ashkenazi Jewishnot grpmax-eligible	22.8%	4
Finnishnot grpmax-eligible	22.7%	4
Middle Eastern	20.8%	5
Amishnot grpmax-eligible	15.7%	6
East Asian	3.9%	26

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.Arg687=
Coding: c.2061G>A
MANE Select: NM_004628
dbSNP: rs2227998
Type: single nucleotide variant
Location: chr3:14152389 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 687: 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 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-arg687 (accessed [today's date]).

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