Is ARX p.Ala511fs (c.1531dup) pathogenic?

ARX p.Ala511fs (c.1531dup) is classified Likely pathogenic in ARX (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with ARX p.Ala511fs (c.1531dup)?

ARX p.Ala511fs (c.1531dup) is associated with developmental and epileptic encephalopathy, 1 (ClinVar).

How common is ARX p.Ala511fs (c.1531dup) in the general population?

ARX p.Ala511fs (c.1531dup) is absent from gnomAD (gnomAD).

How is Infantile epileptic spasms syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ARX p.Ala511fs

c.1531dup · rs2519099351 · VCV3024090

Likely pathogenic Single submitter

Classification

Likely 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

developmental and epileptic encephalopathy, 1

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 7.7	GERP 1.7, 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.Ala511fs
Coding: c.1531dup
MANE Select: NM_139058
dbSNP: rs2519099351
Type: Duplication
Location: chrX:25004827 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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

Disease context

developmental and epileptic encephalopathy, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile epileptic spasms syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant

Similar variants

ARX p.Ala511= Likely benign ★★ same residue
ARX p.Ala105_Ala115dup Pathogenic ★★ same condition
ARX p.Ala109_Ala115dup Pathogenic/Likely pathogenic ★★ same condition
ARX p.Gly397fs Pathogenic/Likely pathogenic ★★ same condition
ARX p.Ala151_Ala152insGlyAlaGlyAlaAlaAlaAlaAlaAlaAlaAla Pathogenic ★ same condition
ARX p.Gly143_Ala153dup Pathogenic ★ same condition
ARX p.Gly482fs Pathogenic ★ same condition
ARX p.Leu324fs 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-ala511fs (accessed [today's date]).

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