Is ARX p.Ala101= (c.303A>G) pathogenic?

ARX p.Ala101= (c.303A>G) is classified Conflicting classifications of pathogenicity in ARX (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0522%, mid); Associated with Inborn genetic diseases.

How common is ARX p.Ala101= (c.303A>G) in the general population?

ARX p.Ala101= (c.303A>G) is ultra-rare (popmax 0.0522%, mid) (gnomAD).

ARX p.Ala101=

Q: What condition is associated with ARX p.Ala101= (c.303A>G)?

ARX p.Ala101= (c.303A>G) is associated with Inborn genetic diseases, intellectual disability, X-linked, with or without seizures, ARX-related, developmental and epileptic encephalopathy, 1 (ClinVar).

c.303A>G · rs797045295 · VCV210325

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0522%, mid)

Conditions

Inborn genetic diseases

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 -2	GERP -1.3
Overall
CADD	6.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0522% Middle Eastern · 1/1,914 alleles

Filtering AF 0.00352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00311%

Overall 0.00534% 47/879,891 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0522%	1,914
Remaining individualsnot grpmax-eligible	0.0225%	4,447
African / African-American	0.0065%	15,377
East Asian	0.00523%	19,125
European (non-Finnish)	0.00485%	20,616

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ARX
Protein: p.Ala101=
Coding: c.303A>G
MANE Select: NM_139058
dbSNP: rs797045295
Type: single nucleotide variant
Location: chrX:25013692 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, X-linked, with or without seizures, ARX-related developmental and epileptic encephalopathy, 1

Similar variants

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
ARX p.Arg371Ter Pathogenic ★★ same condition
ARX p.Arg384Cys Pathogenic/Likely pathogenic ★★ same condition
ARX p.Glu294Ter Pathogenic ★★ same condition
ARX p.Glu308Ter 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-ala101 (accessed [today's date]).

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