ATRX p.Leu1345=
c.4035G>A · rs111725949 · VCV434463
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.023%, mid)
Conditions
2
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 0.13 | GERP -3.5, phastCons 0.93 |
| Overall | ||
| CADD | 5.689 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.023%
Middle Eastern · 1/4,354 alleles
Filtering AF
0.00566%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00405%
Overall
0.000827%
10/1,209,525 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.023% | 4,354 |
| African / African-American | 0.0122% | 8,185 |
| Remaining individualsnot grpmax-eligible | 0.0042% | 23,805 |
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.Leu1345=
- Coding
- c.4035G>A
- MANE Select
- NM_000489
- dbSNP
- rs111725949
- Type
- single nucleotide variant
- Location
- chrX:77663467 (GRCh38)
- Structure
- AlphaFold pLDDT 52.40 · 13 PDB
- Residue 1345
- the 'disordered' region
Similar variants
- ATRX p.Leu1345Phe Conflicting classifications of pathogenicity ★ ⚠ 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-leu1345 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown