Is ARX p.Ala269= (c.807C>T) pathogenic?

ARX p.Ala269= (c.807C>T) is classified Benign/Likely benign in ARX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-02-26). Ultra-rare (popmax 0.0301%, mid); Associated with Inborn genetic diseases.

How common is ARX p.Ala269= (c.807C>T) in the general population?

ARX p.Ala269= (c.807C>T) is ultra-rare (popmax 0.0301%, mid) (gnomAD).

ARX p.Ala269=

Q: What condition is associated with ARX p.Ala269= (c.807C>T)?

ARX p.Ala269= (c.807C>T) is associated with Inborn genetic diseases, corpus callosum agenesis-abnormal genitalia syndrome, X-linked lissencephaly with abnormal genitalia (ClinVar).

c.807C>T · rs587783205 · VCV157762

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0301%, 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 1.4	GERP -1.6, phastCons 0.85
Overall
CADD	7.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0301% Middle Eastern · 1/3,319 alleles

Filtering AF 0.00357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00316%

Overall 0.00407% 48/1,180,065 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0301%	3,319
Remaining individualsnot grpmax-eligible	0.00861%	11,618
European (non-Finnish)	0.00477%	20,971
South Asian	0.00186%	53,860

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.Ala269=
Coding: c.807C>T
MANE Select: NM_139058
dbSNP: rs587783205
Type: single nucleotide variant
Location: chrX:25013188 (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: corpus callosum agenesis-abnormal genitalia syndrome X-linked lissencephaly with abnormal genitalia intellectual disability, X-linked, with or without seizures, ARX-related developmental and epileptic encephalopathy, 1 Partington syndrome

Similar variants

ARX p.Ala269Pro Uncertain significance ★ ⚠ same residue
ARX p.Arg330His Likely pathogenic ★★ same condition
ARX p.Arg332Cys Pathogenic/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

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-ala269 (accessed [today's date]).

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