RYR2 p.Asp680=
c.2040C>T · rs2545835614 · VCV1784891
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Cardiovascular phenotype
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 0.61 | GERP 0.25, phastCons 1 |
| Overall | ||
| CADD | 11.23 | PHRED · no single calibrated threshold — expert panels disagree |
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
- RYR2
- Protein
- p.Asp680=
- Coding
- c.2040C>T
- MANE Select
- NM_001035
- dbSNP
- rs2545835614
- Type
- single nucleotide variant
- Location
- chr1:237496589 (GRCh38)
- Gene constraint
- LOEUF 0.424 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 680
- the b30.2/spry 1 domain; a β-strand
Similar variants
- RYR2 p.Asp680Asn Uncertain significance ★★ same residue
- RYR2 p.Asp680Glu Uncertain significance ★ same residue
- RYR2 p.Asp680Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- RYR2 p.Ala2387Val Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Ala77Val Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Arg169Leu Pathogenic/Likely pathogenic ★★ same condition
- RYR2 p.Arg2401His 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-asp680 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown