RYR1 p.Cys603=
c.1809C>T · rs562647214 · VCV2906230
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
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 0.12 | GERP -2.4, phastCons 0.97 |
| Overall | ||
| CADD | 8.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,080 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000248%
4/1,614,102 alleles · very rare
exomes 3/1,461,854 · genomes 1/152,248 · 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.Cys603=
- Coding
- c.1809C>T
- MANE Select
- NM_000540
- dbSNP
- rs562647214
- Type
- single nucleotide variant
- Location
- chr19:38457514 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 603
- the b30.2/spry 1 domain
Similar variants
- RYR1 p.Cys603Arg Uncertain significance ★ ⚠ same residue
- RYR1 p.Cys603Tyr Uncertain significance ★ ⚠ same residue
- 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
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-cys603 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown