Is ARX p.Val64Ala (c.191T>C) pathogenic?

ARX p.Val64Ala (c.191T>C) is classified Uncertain significance in ARX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-01). AlphaMissense: likely benign (0.1153); Absent from gnomAD v4.1; Associated with ARX-related disorder.

What condition is associated with ARX p.Val64Ala (c.191T>C)?

ARX p.Val64Ala (c.191T>C) is associated with ARX-related disorder (ClinVar).

How common is ARX p.Val64Ala (c.191T>C) in the general population?

ARX p.Val64Ala (c.191T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Val64Ala (c.191T>C)?

AlphaMissense predicts likely benign (score 0.1153) — an in-silico prediction, not a clinical call.

ARX p.Val64Ala

c.191T>C · rs2519109098 · VCV3030868

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1153 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,210,267)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARX-related disorder

Computational evidence

Protein change
AlphaMissense	0.1153	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -5.06	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 6.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,633 bp · p 0.032 · regional, not allelic
Overall
CADD	17.4	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

No allele count reported in gnomAD v4.1 (AN 1,210,267). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARX
Protein: p.Val64Ala
Coding: c.191T>C
MANE Select: NM_139058
dbSNP: rs2519109098
Type: single nucleotide variant
Location: chrX:25015547 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 64: the 'disordered' region

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

Disease context

ARX-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARX p.Val64Leu Uncertain significance ★ ⚠ same residue
ARX p.Arg330His Likely pathogenic ★★ same condition
ARX p.Ser319Ter Pathogenic/Likely pathogenic ★★ same condition
ARX p.Ile29Thr Uncertain significance ★★ ⚠ same condition
ARX p.Arg371Gly Likely pathogenic ★ same condition
ARX p.Glu293Ter Likely pathogenic ★ same condition
ARX c.196+401G>A Uncertain significance ★ same condition
ARX p.Ala216Gly 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/arx-p-val64ala (accessed [today's date]).

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