Is ARX p.Ala469fs (c.1406_1415del) pathogenic?

ARX p.Ala469fs (c.14061415del) is classified Pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-20). Absent from gnomAD; Associated with X-linked spasticity-intellectual disability-epilepsy syndrome.

What condition is associated with ARX p.Ala469fs (c.1406_1415del)?

ARX p.Ala469fs (c.1406_1415del) is associated with X-linked spasticity-intellectual disability-epilepsy syndrome (ClinVar).

How common is ARX p.Ala469fs (c.1406_1415del) in the general population?

ARX p.Ala469fs (c.1406_1415del) is absent from gnomAD (gnomAD).

ARX p.Ala469fs

Q: How is X-linked spasticity-intellectual disability-epilepsy syndrome inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1406_1415del · rs2147320332 · VCV1164076

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 spasticity-intellectual disability-epilepsy syndrome

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (4 of 5, 33 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -0.24, 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.Ala469fs
Coding: c.1406_1415del
MANE Select: NM_139058
dbSNP: rs2147320332
Type: Deletion
Location: chrX:25007144 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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

Disease context

X-linked spasticity-intellectual disability-epilepsy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked spasticity-intellectual disability-epilepsy syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

ARX p.Gly120fs Pathogenic ★★ same type
ARX p.Gly197fs Pathogenic/Likely pathogenic ★★ same type
ARX p.Leu491fs Pathogenic ★★ same type
ARX p.Pro490_Leu491insTer Pathogenic ★★ same type
ARX p.240EEELLEDD[1] Uncertain significance ★★ same type
ARX p.Ala110_Ala115del Uncertain significance ★★ same type
ARX p.Asp140_Ala151del Uncertain significance ★★ same type
ARX p.Ala148_Ala155del Benign/Likely benign ★★ same type

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-ala469fs (accessed [today's date]).

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