Is ARX p.Ala425fs (c.1273_1279del) pathogenic?

ARX p.Ala425fs (c.12731279del) is classified Pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). Absent from gnomAD; Associated with intellectual disability, X-linked, with or without seizures, ARX-related.

How common is ARX p.Ala425fs (c.1273_1279del) in the general population?

ARX p.Ala425fs (c.1273_1279del) is absent from gnomAD (gnomAD).

ARX p.Ala425fs

Q: What condition is associated with ARX p.Ala425fs (c.1273_1279del)?

ARX p.Ala425fs (c.1273_1279del) is associated with intellectual disability, X-linked, with or without seizures, ARX-related, developmental and epileptic encephalopathy, 1 (ClinVar).

c.1273_1279del · rs2519101744 · VCV2953993

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

intellectual disability, X-linked, with or without seizures, ARX-related

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 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, 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.Ala425fs
Coding: c.1273_1279del
MANE Select: NM_139058
dbSNP: rs2519101744
Type: Deletion
Location: chrX:25007280 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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

Disease context

intellectual disability, X-linked, with or without seizures, ARX-related — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 1

Similar variants

ARX p.Ala425= Likely benign ★★ same residue
ARX p.Ala425Thr Uncertain significance ★ ⚠ same residue
ARX p.Gly120fs Pathogenic ★★ same condition
ARX p.Leu491fs Pathogenic ★★ same condition
ARX p.Pro490_Leu491insTer Pathogenic ★★ same condition
ARX p.240EEELLEDD[1] Uncertain significance ★★ same condition
ARX p.Ala110_Ala115del Uncertain significance ★★ same condition
ARX p.Asp140_Ala151del 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-ala425fs (accessed [today's date]).

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