RYR2 p.Asp17=
c.51T>C · rs373674802 · VCV1157467
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0175%, afr)
Conditions
3
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.329 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -4.3 |
| Overall | ||
| CADD | 5.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0175%
African / African-American · 13/74,318 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00819%
Overall
0.00108%
17/1,577,332 alleles · ultra-rare
exomes 7/1,425,122 · genomes 10/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0175% | 5,717 |
| Remaining individualsnot grpmax-eligible | 0.00652% | 15,329 |
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.Asp17=
- Coding
- c.51T>C
- MANE Select
- NM_001035
- dbSNP
- rs373674802
- Type
- single nucleotide variant
- Location
- chr1:237270499 (GRCh38)
- Gene constraint
- LOEUF 0.424 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 17
- a β-strand
Similar variants
- RYR2 p.Asp17Asn Uncertain significance ★★ ⚠ same residue
- RYR2 p.Asp17Gly Uncertain significance ★ ⚠ same residue
- RYR2 p.Asp17Tyr Uncertain significance ★ same residue
- 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
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-asp17 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown