ATRX p.Ala419=
c.1257G>A · rs185550133 · VCV698407
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0592%, eas)
Conditions
1
alpha thalassemia-X-linked intellectual disability syndrome
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 3.4 | GERP -2.8, phastCons 1 |
| Overall | ||
| CADD | 0.939 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0592%
East Asian · 20/33,772 alleles
Filtering AF
0.0392%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0328%
Overall
0.00249%
30/1,206,421 alleles · ultra-rare
exomes 27/1,094,120 · genomes 3/112,301 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0592% | 1,689 |
| South Asian | 0.00352% | 28,380 |
| Remaining individualsnot grpmax-eligible | 0.00211% | 47,500 |
| European (non-Finnish) | 0.000785% | 127,400 |
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
- ATRX
- Protein
- p.Ala419=
- Coding
- c.1257G>A
- MANE Select
- NM_000489
- dbSNP
- rs185550133
- Type
- single nucleotide variant
- Location
- chrX:77683999 (GRCh38)
- Structure
- AlphaFold pLDDT 52.40 · 13 PDB
Similar variants
- ATRX p.Ala419Val Likely benign ★★ same residue
- ATRX c.5449-7A>G Likely pathogenic ★★ same condition
- ATRX p.Arg1022Ter Pathogenic/Likely pathogenic ★★ same condition
- ATRX p.Arg1661Cys Likely pathogenic ★★ ⚠ same condition
- ATRX p.Arg2085Cys Pathogenic/Likely pathogenic ★★ same condition
- ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same condition
- ATRX p.Arg2131Gln Pathogenic/Likely pathogenic ★★ same condition
- ATRX p.Arg2178Trp 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/atrx-p-ala419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown