ATRX p.Arg781Pro
c.2342G>C · VCV4535920
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9511 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9511 | likely pathogenic |
|---|---|---|
| REVEL | 0.58 | indeterminate |
| SaProt | LLR -9.77 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.9, phastCons 1 |
| Regional constraint | o/e 1.31 | unconstrained · MANE · 2,828 bp · p 3.3e-15 · regional, not allelic |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ATRX
- Protein
- p.Arg781Pro
- Coding
- c.2342G>C
- MANE Select
- NM_000489
- Type
- single nucleotide variant
- Location
- chrX:77682914 (GRCh38)
- Structure
- AlphaFold pLDDT 52.40 · 13 PDB
- Residue 781
- the 'disordered' region
Similar variants
- ATRX p.Arg781Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- ATRX p.Arg781= Likely benign ★ same residue
- ATRX c.134-2A>G Pathogenic/Likely pathogenic ★★ same type
- ATRX c.5449-7A>G Likely pathogenic ★★ same type
- ATRX p.Arg1022Ter Pathogenic/Likely pathogenic ★★ same type
- ATRX p.Arg1661Cys Likely pathogenic ★★ ⚠ same type
- ATRX p.Arg2085Cys Pathogenic/Likely pathogenic ★★ same type
- ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same type
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-arg781pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown