RYR2 p.Ala1663=
c.4989C>A · rs147060179 · VCV1384020
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0691%, eas)
Conditions
2
cardiomyopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4 |
| Overall | ||
| CADD | 0.035 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0691%
East Asian · 31/44,886 alleles
Filtering AF
0.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0435%
Overall
0.00192%
31/1,613,898 alleles · ultra-rare
exomes 30/1,461,698 · genomes 1/152,200 · joint denominator
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
- RYR2
- Protein
- p.Ala1663=
- Coding
- c.4989C>A
- MANE Select
- NM_001035
- dbSNP
- rs147060179
- Type
- single nucleotide variant
- Location
- chr1:237614117 (GRCh38)
- Gene constraint
- LOEUF 0.424 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 1663
- the '4 x approximate repeats' region; an α-helix
Similar variants
- RYR2 p.Ala2387Thr Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Ala2387Val Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Ala391Asp Likely pathogenic ★★ same condition
- RYR2 p.Ala4091Val Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Ala4510Pro Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Ala77Val Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Arg176Gln 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/ryr2-p-ala1663 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown