Is ARX p.Glu293Ter (c.877G>T) pathogenic?

ARX p.Glu293Ter (c.877G>T) is classified Likely pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-20). Absent from gnomAD v4.1; Associated with ARX-related disorder.

What condition is associated with ARX p.Glu293Ter (c.877G>T)?

ARX p.Glu293Ter (c.877G>T) is associated with ARX-related disorder (ClinVar).

How common is ARX p.Glu293Ter (c.877G>T) in the general population?

ARX p.Glu293Ter (c.877G>T) is absent from gnomAD v4.1 (gnomAD).

ARX p.Glu293Ter

c.877G>T · VCV4949446

Likely pathogenic Single submitter

Classification

Likely 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 1,202,910)

Conditions

ARX-related disorder

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 2 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.6, phastCons 1
Overall
CADD	37.0	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 1,202,910). 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.Glu293Ter
Coding: c.877G>T
MANE Select: NM_139058
Type: single nucleotide variant
Location: chrX:25013118 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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.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 c.196+401G>A Uncertain significance ★ same condition
ARX p.Ala216Gly Uncertain significance ⚠ same condition
ARX p.Tyr27Cys Uncertain significance ⚠ same condition
ARX p.Val64Ala 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-glu293ter (accessed [today's date]).

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