RYR1 p.Pro2139=
c.6417G>A · rs780880695 · VCV1087774
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
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 -3.7 | GERP -4.9 |
| Overall | ||
| CADD | 2.659 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,878 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000434%
7/1,613,358 alleles · very rare
exomes 7/1,461,028 · genomes 0/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,439 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,231 |
| South Asian | 0.0022% | 45,525 |
| European (non-Finnish) | 8.47e-05% | 1,180,032 |
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.Pro2139=
- Coding
- c.6417G>A
- MANE Select
- NM_000540
- dbSNP
- rs780880695
- Type
- single nucleotide variant
- Location
- chr19:38494494 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 2139
- the '6 x approximate repeats' region
Similar variants
- RYR1 p.Pro2139Gln Uncertain significance ★ same residue
- RYR1 p.Pro2139Leu 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-pro2139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown