Is ARX p.Ile32Met (c.96C>G) pathogenic?

ARX p.Ile32Met (c.96C>G) is classified Uncertain significance in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-19). AlphaMissense: likely pathogenic (0.9917); Absent from gnomAD v4.1.

How common is ARX p.Ile32Met (c.96C>G) in the general population?

ARX p.Ile32Met (c.96C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Ile32Met (c.96C>G)?

AlphaMissense predicts likely pathogenic (score 0.9917) — an in-silico prediction, not a clinical call.

ARX p.Ile32Met

c.96C>G · rs2519109248 · VCV2504160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9917 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9917	likely pathogenic
REVEL	0.557	indeterminate
SaProt	LLR -12.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.73, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,633 bp · p 0.032 · regional, not allelic
Overall
CADD	23.8	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: ARX
Protein: p.Ile32Met
Coding: c.96C>G
MANE Select: NM_139058
dbSNP: rs2519109248
Type: single nucleotide variant
Location: chrX:25015642 (GRCh38)
Structure: AlphaFold pLDDT 56.51

Full ARX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARX p.Arg330His Likely pathogenic ★★ same type
ARX p.Arg332Cys Pathogenic/Likely pathogenic ★★ same type
ARX p.Arg332Gly Pathogenic/Likely pathogenic ★★ same type
ARX p.Arg332His Pathogenic ★★ same type
ARX p.Arg371Gln Likely pathogenic ★★ same type
ARX p.Arg371Ter Pathogenic ★★ same type
ARX p.Arg384Cys Pathogenic/Likely pathogenic ★★ same type
ARX p.Cys10Ter 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/arx-p-ile32met (accessed [today's date]).

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