Is XPC p.Ile182Arg (c.545T>G) pathogenic?

XPC p.Ile182Arg (c.545T>G) is classified Uncertain significance in XPC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-03). AlphaMissense: likely benign (0.1281); Absent from gnomAD v4.1.

How common is XPC p.Ile182Arg (c.545T>G) in the general population?

XPC p.Ile182Arg (c.545T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about XPC p.Ile182Arg (c.545T>G)?

AlphaMissense predicts likely benign (score 0.1281) — an in-silico prediction, not a clinical call.

XPC p.Ile182Arg

c.545T>G · rs868302213 · VCV1163243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1281 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1281	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -7.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.77, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.33 · regional, not allelic
Overall
CADD	14.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ile182Arg
Coding: c.545T>G
MANE Select: NM_004628
dbSNP: rs868302213
Type: single nucleotide variant
Location: chr3:14167245 (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 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
XPC c.413-24A>G Pathogenic/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-ile182arg (accessed [today's date]).

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