Is XPC p.Cys377= (c.1131C>T) pathogenic?

XPC p.Cys377= (c.1131C>T) is classified Conflicting classifications of pathogenicity in XPC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-06). Very rare (popmax 0.00509%, nfe); Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Cys377= (c.1131C>T)?

XPC p.Cys377= (c.1131C>T) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Cys377= (c.1131C>T) in the general population?

XPC p.Cys377= (c.1131C>T) is very rare (popmax 0.00509%, nfe) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

XPC p.Cys377=

c.1131C>T · rs187340581 · VCV343575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00509%, nfe)

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 0.56	GERP 0.53
Overall
CADD	1.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00509% European (non-Finnish) · 60/1,179,872 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00384% 62/1,613,900 alleles · very rare exomes 58/1,461,704 · genomes 4/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00509%	19,665
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	75,028

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.Cys377=
Coding: c.1131C>T
MANE Select: NM_004628
dbSNP: rs187340581
Type: single nucleotide variant
Location: chr3:14158752 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 377: the 'disordered' region

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-cys377 (accessed [today's date]).

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