Is PRKAG2 p.Pro366= (c.1098A>G) pathogenic?

PRKAG2 p.Pro366= (c.1098A>G) is classified Conflicting classifications of pathogenicity in PRKAG2 (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-02-03). Rare (popmax 0.586%, afr); Associated with Cardiovascular phenotype.

What condition is associated with PRKAG2 p.Pro366= (c.1098A>G)?

PRKAG2 p.Pro366= (c.1098A>G) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is PRKAG2 p.Pro366= (c.1098A>G) in the general population?

PRKAG2 p.Pro366= (c.1098A>G) is rare (popmax 0.586%, afr) (gnomAD).

PRKAG2 p.Pro366=

c.1098A>G · rs116541276 · VCV45686

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.586%, afr)

Conditions

Cardiovascular phenotype

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 1.9	GERP 1.5, phastCons 1
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.586% African / African-American · 438/74,790 alleles

Filtering AF 0.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.523%

Overall 0.0299% 479/1,600,920 alleles · rare exomes 229/1,448,572 · genomes 250/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.586%	171
Admixed American	0.0319%	3,133
Remaining individualsnot grpmax-eligible	0.0259%	3,860
Middle Eastern	0.0167%	5,982
South Asian	0.00111%	90,236
European (non-Finnish)	0.000341%	292,955

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.Pro366=
Coding: c.1098A>G
MANE Select: NM_016203
dbSNP: rs116541276
Type: single nucleotide variant
Location: chr7:151570179 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 366: the cbs 2 domain

Full PRKAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy Wolff-Parkinson-White syndrome lethal congenital glycogen storage disease of heart hypertrophic cardiomyopathy 6

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-pro366 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown