Is XPC p.Val545Ala (c.1634T>C) pathogenic?

XPC p.Val545Ala (c.1634T>C) is classified Uncertain significance in XPC (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-17). AlphaMissense: ambiguous (0.4006); Absent from gnomAD v4.1; Associated with xeroderma pigmentosum group C.

What condition is associated with XPC p.Val545Ala (c.1634T>C)?

XPC p.Val545Ala (c.1634T>C) is associated with xeroderma pigmentosum group C (ClinVar).

How common is XPC p.Val545Ala (c.1634T>C) in the general population?

XPC p.Val545Ala (c.1634T>C) is absent from gnomAD v4.1 (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.Val545Ala (c.1634T>C)?

AlphaMissense predicts ambiguous (score 0.4006) — an in-silico prediction, not a clinical call.

XPC p.Val545Ala

c.1634T>C · rs1696004839 · VCV903381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4006 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

xeroderma pigmentosum group C

Computational evidence

Protein change
AlphaMissense	0.4006	ambiguous
REVEL	0.441	indeterminate
SaProt	LLR -11.23	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.33 · regional, not allelic
Overall
CADD	25.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: XPC
Protein: p.Val545Ala
Coding: c.1634T>C
MANE Select: NM_004628
dbSNP: rs1696004839
Type: single nucleotide variant
Location: chr3:14158249 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB
Residue 545: the 'interaction with rad23b' 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-val545ala (accessed [today's date]).

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