RYR1 p.Pro1106=
c.3318C>G · rs377584912 · VCV1089714
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000508%, nfe)
Conditions
2
RYR1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -3.4 |
| Overall | ||
| CADD | 0.772 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000508%
European (non-Finnish) · 6/1,180,048 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,614,064 alleles · very rare
exomes 4/1,461,870 · genomes 2/152,194 · 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.Pro1106=
- Coding
- c.3318C>G
- MANE Select
- NM_000540
- dbSNP
- rs377584912
- Type
- single nucleotide variant
- Location
- chr19:38467749 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1106
- the b30.2/spry 2 domain; the '6 x approximate repeats' region
Similar variants
- 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
- RYR1 p.Ala2437Val 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-pro1106 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown