Is ARX p.Asp30Tyr (c.88G>T) pathogenic?

ARX p.Asp30Tyr (c.88G>T) is classified Uncertain significance in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). AlphaMissense: likely pathogenic (0.9989); Absent from gnomAD v4.1; Associated with epileptic encephalopathy, early infanitle, 1.

What condition is associated with ARX p.Asp30Tyr (c.88G>T)?

ARX p.Asp30Tyr (c.88G>T) is associated with epileptic encephalopathy, early infanitle, 1 (ClinVar).

How common is ARX p.Asp30Tyr (c.88G>T) in the general population?

ARX p.Asp30Tyr (c.88G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Asp30Tyr (c.88G>T)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

ARX p.Asp30Tyr

c.88G>T · rs587783207 · VCV157764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epileptic encephalopathy, early infanitle, 1

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 7% in ARX
REVEL	0.738	pathogenic-leaning
SaProt	LLR -15.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,633 bp · p 0.032 · regional, not allelic
Overall
CADD	26.8	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.Asp30Tyr
Coding: c.88G>T
MANE Select: NM_139058
dbSNP: rs587783207
Type: single nucleotide variant
Location: chrX:25015650 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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

Disease context

epileptic encephalopathy, early infanitle, 1

Similar variants

ARX p.Asp30Asn Uncertain significance ★ ⚠ same residue
ARX p.Asp30Glu Uncertain significance ★ ⚠ same residue
ARX p.Arg371Ter Pathogenic ★★ same condition
ARX p.Glu12Ter Pathogenic ★ same condition
ARX p.Thr333Ser Pathogenic ★ same condition
ARX p.Arg483Lys Uncertain significance ★ ⚠ same condition
ARX p.Gly197fs Pathogenic/Likely pathogenic ★★ same condition
ARX c.196+129_1073+903del 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-asp30tyr (accessed [today's date]).

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