ALYREF p.Arg231Leu
c.692G>T · VCV3351628
Uncertain significance
No assertion criteria
Classification
Uncertain significance
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00178%, nfe)
Conditions
1
ALYREF-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.464 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 0.64, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 422 bp · p 0.81 · regional, not allelic |
| Overall | ||
| CADD | 23.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
European (non-Finnish) · 21/1,179,102 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.00144%
21/1,453,552 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
- ALYREF
- Protein
- p.Arg231Leu
- Coding
- c.692G>T
- MANE Select
- NM_005782
- Type
- single nucleotide variant
- Location
- chr17:81888329 (GRCh38)
- Gene constraint
- LOEUF 0.235 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 65.65 · 4 PDB
- Residue 231
- the 'disordered' region; the 'rna-binding domain 2' region
Disease context
ALYREF-related disorder
Similar variants
- ALYREF p.Pro2His Uncertain significance ★ same condition
- ALYREF p.Leu16= Likely benign same condition
- ALYREF p.Gln253Glu Uncertain significance ★ same type
- ALYREF p.Ser4Phe Uncertain significance ★ same type
- ALYREF p.Ser201= Likely benign ★ 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/alyref-p-arg231leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown