Is ARX p.Ala518fs (c.1552del) pathogenic?

ARX p.Ala518fs (c.1552del) is classified Likely pathogenic in ARX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2002-09-08). Absent from gnomAD; Associated with intellectual disability, X-linked, with or without seizures, ARX-related.

What condition is associated with ARX p.Ala518fs (c.1552del)?

ARX p.Ala518fs (c.1552del) is associated with intellectual disability, X-linked, with or without seizures, ARX-related (ClinVar).

How common is ARX p.Ala518fs (c.1552del) in the general population?

ARX p.Ala518fs (c.1552del) is absent from gnomAD (gnomAD).

ARX p.Ala518fs

c.1552del · rs2519099311 · VCV1704275

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

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	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP -0.19, 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.Ala518fs
Coding: c.1552del
MANE Select: NM_139058
dbSNP: rs2519099311
Type: Deletion
Location: chrX:25004807 (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

Similar variants

ARX p.Gly120fs 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
ARX p.Ala148_Ala155del Benign/Likely benign ★★ same condition
ARX p.Ala151_Ala155del Benign ★★ same condition
ARX p.Gly143_Ala150del Benign/Likely benign ★★ 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-ala518fs (accessed [today's date]).

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