Is ARX p.Phe335fs (c.1002_1007delinsTGTACCA) pathogenic?

ARX p.Phe335fs (c.10021007delinsTGTACCA) is classified Pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2014-01-09). Absent from gnomAD; Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with ARX p.Phe335fs (c.1002_1007delinsTGTACCA)?

ARX p.Phe335fs (c.1002_1007delinsTGTACCA) is associated with developmental and epileptic encephalopathy, 1 (ClinVar).

How common is ARX p.Phe335fs (c.1002_1007delinsTGTACCA) in the general population?

ARX p.Phe335fs (c.1002_1007delinsTGTACCA) 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.Phe335fs

c.1002_1007delinsTGTACCA · rs869312662 · VCV224076

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

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	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.1, 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.Phe335fs
Coding: c.1002_1007delinsTGTACCA
MANE Select: NM_139058
dbSNP: rs869312662
Type: Indel
Location: chrX:25012988 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 335: a DNA-binding region

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.Phe335= Likely benign ★ same residue
ARX c.197-4_197-3delinsAA Uncertain significance ★ same condition
ARX p.Ala105_Ala115dup Pathogenic ★★ same condition
ARX p.Ala108_Ala115dup Pathogenic ★★ same condition
ARX p.Ala109_Ala115dup Pathogenic/Likely pathogenic ★★ same condition
ARX p.Arg330His Likely pathogenic ★★ same condition
ARX p.Arg332Gly Pathogenic/Likely pathogenic ★★ same condition
ARX p.Arg332His 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-phe335fs (accessed [today's date]).

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