ATRX p.Leu274=
c.820T>C · rs146012355 · VCV696700
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0297%, afr)
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 2.2 | GERP -1.4, phastCons 0.67 |
| Overall | ||
| CADD | 5.977 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0297%
African / African-American · 17/57,319 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0155%
Overall
0.00273%
33/1,210,353 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0297% | 3,372 |
| European (non-Finnish) | 0.00179% | 55,953 |
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.Leu274=
- Coding
- c.820T>C
- MANE Select
- NM_000489
- dbSNP
- rs146012355
- Type
- single nucleotide variant
- Location
- chrX:77684436 (GRCh38)
- Structure
- AlphaFold pLDDT 52.40 · 13 PDB
- Residue 274
- the add domain; an α-helix
Similar variants
- 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
- ATRX p.Arg2386Ter 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-leu274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown