Is XPC p.Arg247Ter (c.739C>T) pathogenic?

XPC p.Arg247Ter (c.739C>T) is classified Pathogenic in XPC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-14). Very rare (popmax 0.00673%, eas); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Arg247Ter (c.739C>T)?

XPC p.Arg247Ter (c.739C>T) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Arg247Ter (c.739C>T) in the general population?

XPC p.Arg247Ter (c.739C>T) is very rare (popmax 0.00673%, eas) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

XPC p.Arg247Ter

c.739C>T · rs764321665 · VCV556301

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00673%, eas)

Conditions

xeroderma pigmentosum group C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -3.4
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00673% East Asian · 3/44,600 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000894%

Overall 0.000624% 10/1,603,198 alleles · very rare exomes 8/1,451,036 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00673%	14,867
Admixed American	0.00171%	58,320
Remaining individualsnot grpmax-eligible	0.00161%	62,144
European (non-Finnish)	0.000426%	234,961

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.Arg247Ter
Coding: c.739C>T
MANE Select: NM_004628
dbSNP: rs764321665
Type: single nucleotide variant
Location: chr3:14165468 (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 p.Arg247Gln Likely benign ★ same residue
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

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-arg247ter (accessed [today's date]).

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