ARX p.Ala258=
c.774G>C · rs2048709739 · VCV2940557
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00195%, nfe)
Conditions
2
intellectual disability, X-linked, with or without seizures, ARX-related
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 -0.29 | GERP -3.1, phastCons 0.26 |
| Overall | ||
| CADD | 6.015 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00195%
European (non-Finnish) · 17/872,434 alleles
Filtering AF
0.00119%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00097%
Overall
0.00162%
17/1,050,446 alleles · very rare
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.Ala258=
- Coding
- c.774G>C
- MANE Select
- NM_139058
- dbSNP
- rs2048709739
- Type
- single nucleotide variant
- Location
- chrX:25013221 (GRCh38)
- Structure
- AlphaFold pLDDT 56.51
Similar variants
- ARX p.Ala258Glu Uncertain significance ★★ ⚠ 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
- ARX p.Arg371Ter Pathogenic ★★ same condition
- ARX p.Arg384Cys Pathogenic/Likely pathogenic ★★ same condition
- ARX p.Glu294Ter 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-ala258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown