PRKAG2 p.Pro216=
c.648A>G · rs751742816 · VCV1331903
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Conditions
3
cardiomyopathy
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 -9.5 | GERP -3.2 |
| Overall | ||
| CADD | 0.267 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,908 alleles
Overall
6.2e-05%
1/1,613,990 alleles · very rare
exomes 0/1,461,872 · genomes 1/152,118 · 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
- PRKAG2
- Protein
- p.Pro216=
- Coding
- c.648A>G
- MANE Select
- NM_016203
- dbSNP
- rs751742816
- Type
- single nucleotide variant
- Location
- chr7:151675456 (GRCh38)
- Gene constraint
- LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.24
- Residue 216
- the 'disordered' region
Similar variants
- PRKAG2 p.Arg302Gln Pathogenic ★★ same condition
- PRKAG2 p.Arg302Pro Pathogenic/Likely pathogenic ★★ same condition
- PRKAG2 p.Arg531Gln Pathogenic ★★ same condition
- PRKAG2 p.Glu506Gln Likely pathogenic ★★ same condition
- PRKAG2 p.His530Arg Pathogenic ★★ same condition
- PRKAG2 p.Phe293Leu Pathogenic/Likely pathogenic ★★ same condition
- PRKAG2 p.Thr400Asn Likely pathogenic ★★ same condition
- PRKAG2 c.1005+6T>C 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/prkag2-p-pro216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown