Is XPC p.Arg307Trp (c.919C>T) pathogenic?

XPC p.Arg307Trp (c.919C>T) is classified Uncertain significance in XPC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-29). AlphaMissense: ambiguous (0.5174); Very rare (popmax 0.00725%, eas); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Arg307Trp (c.919C>T)?

XPC p.Arg307Trp (c.919C>T) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Arg307Trp (c.919C>T) in the general population?

XPC p.Arg307Trp (c.919C>T) is very rare (popmax 0.00725%, eas) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

What do computational predictors say about XPC p.Arg307Trp (c.919C>T)?

AlphaMissense predicts ambiguous (score 0.5174) — an in-silico prediction, not a clinical call.

XPC p.Arg307Trp

c.919C>T · rs367961191 · VCV2431722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00725%, eas)

Conditions

xeroderma pigmentosum group C

Computational evidence

Protein change
AlphaMissense	0.5174	ambiguous
REVEL	0.56	indeterminate
SaProt	LLR -12.90	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.33 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00725% East Asian · 3/41,380 alleles

Filtering AF 0.00192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00225% 35/1,557,126 alleles · very rare exomes 29/1,404,850 · genomes 6/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00725%	13,793
Admixed American	0.00387%	25,845
South Asian	0.00237%	42,146
European (non-Finnish)	0.00226%	44,233
Remaining individualsnot grpmax-eligible	0.00165%	60,434
African / African-American	0.00136%	73,348

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.Arg307Trp
Coding: c.919C>T
MANE Select: NM_004628
dbSNP: rs367961191
Type: single nucleotide variant
Location: chr3:14159812 (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-arg307trp (accessed [today's date]).

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