Is ARX p.Ala115= (c.345C>G) pathogenic?

ARX p.Ala115= (c.345C>G) is classified Likely benign in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-11). Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with ARX p.Ala115= (c.345C>G)?

ARX p.Ala115= (c.345C>G) is associated with developmental and epileptic encephalopathy, 1, intellectual disability, X-linked, with or without seizures, ARX-related (ClinVar).

How common is ARX p.Ala115= (c.345C>G) in the general population?

ARX p.Ala115= (c.345C>G) is absent from gnomAD v4.1 (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.Ala115=

c.345C>G · rs2147324328 · VCV1112422

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 765,984)

Conditions

developmental and epileptic encephalopathy, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.88, phastCons 0.99
Overall
CADD	8.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 765,984). 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.Ala115=
Coding: c.345C>G
MANE Select: NM_139058
dbSNP: rs2147324328
Type: single nucleotide variant
Location: chrX:25013650 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 115: a UniProt-annotated variant site (in dee1)

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

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

For Infantile epileptic spasms syndrome (Orphanet):

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

Similar variants

ARX p.Ala115_Thr116insAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAla Uncertain significance ★ same residue
ARX p.Ala115del Uncertain significance ★ same residue
ARX p.Ala115dup Conflicting classifications of pathogenicity ★ same residue
ARX p.Ala115_Thr116insAla Likely benign ★ same residue
ARX p.Arg330His Likely pathogenic ★★ same condition
ARX p.Arg332Gly Pathogenic/Likely pathogenic ★★ same condition
ARX p.Arg332His Pathogenic ★★ same condition
ARX p.Arg371Gln Likely 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-ala115 (accessed [today's date]).

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