Is ARX p.Ala151Val (c.452C>T) pathogenic?

ARX p.Ala151Val (c.452C>T) is classified Uncertain significance in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-10). AlphaMissense: likely benign (0.2112); Very rare (popmax 0.000596%, nfe); Associated with intellectual disability, X-linked, with or without seizures, ARX-related.

How common is ARX p.Ala151Val (c.452C>T) in the general population?

ARX p.Ala151Val (c.452C>T) is very rare (popmax 0.000596%, nfe) (gnomAD).

What do computational predictors say about ARX p.Ala151Val (c.452C>T)?

AlphaMissense predicts likely benign (score 0.2112) — an in-silico prediction, not a clinical call.

ARX p.Ala151Val

Q: What condition is associated with ARX p.Ala151Val (c.452C>T)?

ARX p.Ala151Val (c.452C>T) is associated with intellectual disability, X-linked, with or without seizures, ARX-related, developmental and epileptic encephalopathy, 1 (ClinVar).

c.452C>T · rs1439646032 · VCV1369936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2112 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000596%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked, with or without seizures, ARX-related

Computational evidence

Protein change
AlphaMissense	0.2112	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -9.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.87	unconstrained · MANE · 2,633 bp · p 0.032 · regional, not allelic
Overall
CADD	13.8	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

Grpmax group 0.000596% European (non-Finnish) · 4/671,271 alleles

Filtering AF 0.000139% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.4e-05%

Overall 0.000579% 4/690,620 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ARX
Protein: p.Ala151Val
Coding: c.452C>T
MANE Select: NM_139058
dbSNP: rs1439646032
Type: single nucleotide variant
Location: chrX:25013543 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 151: the 'disordered' region

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

Disease context

intellectual disability, X-linked, with or without seizures, ARX-related — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 1

Similar variants

ARX p.Ala151= Likely benign ★★ same residue
ARX p.Ala151_Ala155del Benign ★★ same residue
ARX p.Ala151_Ala152insGlyAlaGlyAlaAlaAlaAlaAlaAlaAlaAla Pathogenic ★ same residue
ARX p.Ala151fs Pathogenic ★ same residue
ARX p.Arg330His Likely pathogenic ★★ same condition
ARX p.Arg332Gly Pathogenic/Likely pathogenic ★★ same condition
ARX p.Arg332His Pathogenic ★★ same condition
ARX p.Arg371Gln Likely pathogenic ★★ 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-ala151val (accessed [today's date]).

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