Is ARX p.Glu12Ter (c.34G>T) pathogenic?

ARX p.Glu12Ter (c.34G>T) is classified Pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). Absent from gnomAD v4.1; Associated with epileptic encephalopathy, early infanitle, 1.

What condition is associated with ARX p.Glu12Ter (c.34G>T)?

ARX p.Glu12Ter (c.34G>T) is associated with epileptic encephalopathy, early infanitle, 1 (ClinVar).

How common is ARX p.Glu12Ter (c.34G>T) in the general population?

ARX p.Glu12Ter (c.34G>T) is absent from gnomAD v4.1 (gnomAD).

ARX p.Glu12Ter

c.34G>T · rs587783200 · VCV157757

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,202,809)

Conditions

epileptic encephalopathy, early infanitle, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,202,809). 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.Glu12Ter
Coding: c.34G>T
MANE Select: NM_139058
dbSNP: rs587783200
Type: single nucleotide variant
Location: chrX:25015704 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 12: the 'disordered' region

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.Glu12Lys Uncertain significance ★ ⚠ same residue
ARX p.Arg371Ter Pathogenic ★★ same condition
ARX p.Thr333Ser Pathogenic ★ same condition
ARX p.Arg483Lys Uncertain significance ★ ⚠ same condition
ARX p.Asp30Tyr Uncertain significance ★ ⚠ same condition
ARX p.Gly197fs Pathogenic/Likely pathogenic ★★ same condition
ARX c.196+129_1073+903del Pathogenic ★ same condition
ARX p.Gly515fs 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-glu12ter (accessed [today's date]).

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