RYR1 p.Phe2425=
c.7275C>T · rs2514315641 · VCV2578824
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
1
RYR1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP -0.82, phastCons 1 |
| Overall | ||
| CADD | 9.728 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,010 alleles
Overall
6.2e-05%
1/1,614,156 alleles · very rare
exomes 1/1,461,858 · genomes 0/152,298 · 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
- RYR1
- Protein
- p.Phe2425=
- Coding
- c.7275C>T
- MANE Select
- NM_000540
- dbSNP
- rs2514315641
- Type
- single nucleotide variant
- Location
- chr19:38499968 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 2425
- the '6 x approximate repeats' region
Similar variants
- RYR1 c.10627-1G>C Pathogenic/Likely pathogenic ★★ same condition
- RYR1 c.14647-1G>C Likely pathogenic ★★ same condition
- RYR1 c.14869-1G>T Pathogenic/Likely pathogenic ★★ same condition
- RYR1 c.2683-1G>A Pathogenic/Likely pathogenic ★★ same condition
- RYR1 c.2870+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RYR1 c.3381+1G>A Pathogenic ★★ same condition
- RYR1 c.4935-2A>T Likely pathogenic ★★ same condition
- RYR1 c.6127+1G>A 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/ryr1-p-phe2425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown