RYR1 p.Phe2425del
c.7274_7276del · VCV4757638
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
malignant hyperthermia, susceptibility to, 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 17.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,920 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000124%
2/1,613,996 alleles · very rare
exomes 1/1,461,832 · genomes 1/152,164 · 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.Phe2425del
- Coding
- c.7274_7276del
- MANE Select
- NM_000540
- Type
- Deletion
- Location
- chr19:38499965 (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.958-11del Likely benign ★★★ same condition
- RYR1 p.Ala1671fs Likely pathogenic ★★ same condition
- RYR1 p.Glu4327fs Pathogenic/Likely pathogenic ★★ same condition
- RYR1 c.1244+6del Uncertain significance ★★ same condition
- RYR1 c.14868+5del Uncertain significance ★★ same condition
- RYR1 c.9233+6del Uncertain significance ★★ same condition
- RYR1 c.957+5_957+29del Uncertain significance ★★ same condition
- RYR1 p.Ala4268_Ala4272del Uncertain significance ★★ 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-phe2425del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown