Is XPC p.Phe302Val (c.904T>G) pathogenic?

XPC p.Phe302Val (c.904T>G) is classified Uncertain significance in XPC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.5251); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with XPC p.Phe302Val (c.904T>G)?

XPC p.Phe302Val (c.904T>G) is associated with Inborn genetic diseases (ClinVar).

How common is XPC p.Phe302Val (c.904T>G) in the general population?

XPC p.Phe302Val (c.904T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about XPC p.Phe302Val (c.904T>G)?

AlphaMissense predicts ambiguous (score 0.5251) — an in-silico prediction, not a clinical call.

XPC p.Phe302Val

c.904T>G · rs928444044 · VCV2253515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5251	ambiguous
REVEL	0.608	indeterminate
SaProt	LLR -10.03	damaging
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.33 · regional, not allelic
Overall
CADD	26.9	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.Phe302Val
Coding: c.904T>G
MANE Select: NM_004628
dbSNP: rs928444044
Type: single nucleotide variant
Location: chr3:14159827 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

XPC p.Phe302= Likely benign ★ same residue
XPC p.Ala341Gly Uncertain significance ★★ ⚠ same condition
XPC p.Ala341Val Uncertain significance ★★ ⚠ same condition
XPC p.Arg393Gln Uncertain significance ★★ ⚠ same condition
XPC p.Arg858Gly Uncertain significance ★★ same condition
XPC p.Asp885Glu Uncertain significance ★★ ⚠ same condition
XPC p.Gly64Glu Uncertain significance ★★ ⚠ same condition
XPC p.Gly866Arg Uncertain significance ★★ ⚠ 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-phe302val (accessed [today's date]).

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