Is ARX p.Asp366fs (c.1096del) pathogenic?

ARX p.Asp366fs (c.1096del) is classified Pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2015-04-16). Absent from gnomAD; Associated with X-linked lissencephaly with abnormal genitalia.

What condition is associated with ARX p.Asp366fs (c.1096del)?

ARX p.Asp366fs (c.1096del) is associated with X-linked lissencephaly with abnormal genitalia (ClinVar).

How common is ARX p.Asp366fs (c.1096del) in the general population?

ARX p.Asp366fs (c.1096del) is absent from gnomAD (gnomAD).

ARX p.Asp366fs

c.1096del · rs797045289 · VCV210316

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked lissencephaly with abnormal genitalia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Asp366fs
Coding: c.1096del
MANE Select: NM_139058
dbSNP: rs797045289
Type: Deletion
Location: chrX:25010283 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 366: a DNA-binding region

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

Disease context

X-linked lissencephaly with abnormal genitalia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARX p.Ala112fs Pathogenic ★ same condition
ARX p.Ala142fs Pathogenic ★ same condition
ARX p.Ala145fs Likely pathogenic ★ same condition
ARX p.Ala381fs Pathogenic ★ same condition
ARX p.Ala458fs Pathogenic ★ same condition
ARX p.Ala489fs Pathogenic ★ same condition
ARX p.Ala52fs Pathogenic ★ same condition
ARX p.Arg264fs 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-asp366fs (accessed [today's date]).

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