RYR1 p.Ser1663=
c.4989G>A · rs367971361 · VCV3071199
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9 | GERP -4.9 |
| Overall | ||
| CADD | 1.149 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,992 alleles
Overall
0.000124%
2/1,610,288 alleles · very rare
exomes 1/1,458,152 · genomes 1/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,992 |
| European (non-Finnish) | 8.48e-05% | 1,179,926 |
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.Ser1663=
- Coding
- c.4989G>A
- MANE Select
- NM_000540
- dbSNP
- rs367971361
- Type
- single nucleotide variant
- Location
- chr19:38485644 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1663
- the '6 x approximate repeats' region
Similar variants
- RYR1 p.Ser1663Trp Uncertain significance ★★ same residue
- RYR1 c.10347+1G>A Pathogenic ★★★ same condition
- RYR1 c.10348-6C>G Pathogenic ★★★ same condition
- RYR1 c.1925+1G>C Likely pathogenic ★★★ same condition
- RYR1 c.8310+1G>T Pathogenic ★★★ same condition
- RYR1 c.9472+1G>A Pathogenic ★★★ same condition
- RYR1 p.Ala152Asp Likely pathogenic ★★★ same condition
- RYR1 p.Ala2200Val 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-ser1663 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown