Is XPC p.Phe241Ser (c.722T>C) pathogenic?

XPC p.Phe241Ser (c.722T>C) is classified Uncertain significance in XPC (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). AlphaMissense: likely pathogenic (0.9156); Absent from gnomAD v4.1.

How common is XPC p.Phe241Ser (c.722T>C) in the general population?

XPC p.Phe241Ser (c.722T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about XPC p.Phe241Ser (c.722T>C)?

AlphaMissense predicts likely pathogenic (score 0.9156) — an in-silico prediction, not a clinical call.

XPC p.Phe241Ser

c.722T>C · VCV4885460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9156 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9156	likely pathogenic · top 8% in XPC
REVEL	0.445	indeterminate
SaProt	LLR -13.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
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	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Phe241Ser
Coding: c.722T>C
MANE Select: NM_004628
Type: single nucleotide variant
Location: chr3:14165485 (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

Similar variants

XPC p.Phe241= Likely benign ★ same residue
XPC c.104-2A>G Likely pathogenic ★★ same type
XPC c.1872+1G>A Likely pathogenic ★★ same type
XPC c.1872+1G>C Pathogenic/Likely pathogenic ★★ same type
XPC c.2033+1G>A Pathogenic/Likely pathogenic ★★ same type
XPC c.2251-1G>C Pathogenic ★★ same type
XPC c.2420+2T>C Pathogenic/Likely pathogenic ★★ same type
XPC c.299+1G>A Likely pathogenic ★★ same type

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-phe241ser (accessed [today's date]).

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