ARX p.Pro448=
c.1344G>C · rs771296831 · VCV2928830
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000345%, 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 -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000345%
European (non-Finnish) · 3/870,772 alleles
Filtering AF
9.2e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.5e-05%
Overall
0.000288%
3/1,043,061 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.Pro448=
- Coding
- c.1344G>C
- MANE Select
- NM_139058
- dbSNP
- rs771296831
- Type
- single nucleotide variant
- Location
- chrX:25007215 (GRCh38)
- Structure
- AlphaFold pLDDT 56.51
Similar variants
- ARX p.Pro448Ser 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-pro448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown