RYR2 p.Pro990=
c.2970A>G · rs944622392 · VCV922872
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Conditions
1
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 -6.9 | GERP -4.7 |
| Overall | ||
| CADD | 0.062 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,894 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,614,012 alleles · very rare
exomes 3/1,461,690 · genomes 0/152,322 · 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.Pro990=
- Coding
- c.2970A>G
- MANE Select
- NM_001035
- dbSNP
- rs944622392
- Type
- single nucleotide variant
- Location
- chr1:237548494 (GRCh38)
- Gene constraint
- LOEUF 0.424 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 990
- the '4 x approximate repeats' region; an α-helix
Similar variants
- RYR2 p.Pro990Gln Uncertain significance ★★ same residue
- RYR2 p.Pro990Leu Uncertain significance ★★ same residue
- RYR2 p.Pro990Ala Uncertain significance ★ ⚠ same residue
- RYR2 p.Arg420Trp Pathogenic ★★ same condition
- RYR2 p.Arg4497Cys Pathogenic ★★ same condition
- RYR2 p.Asn4763Ser Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Gly357Ser Pathogenic ★★ same condition
- RYR2 p.Met3978Ile 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/ryr2-p-pro990 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown