Is PRKAG2 p.Pro197= (c.591C>T) pathogenic?

PRKAG2 p.Pro197= (c.591C>T) is classified Benign/Likely benign in PRKAG2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-05). Very rare (popmax 0.0022%, sas); Associated with Cardiovascular phenotype.

What condition is associated with PRKAG2 p.Pro197= (c.591C>T)?

PRKAG2 p.Pro197= (c.591C>T) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is PRKAG2 p.Pro197= (c.591C>T) in the general population?

PRKAG2 p.Pro197= (c.591C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

PRKAG2 p.Pro197=

c.591C>T · rs587781126 · VCV138810

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Cardiovascular phenotype

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 -1.2	GERP -3.2
Overall
CADD	4.258	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,094 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000991% 16/1,614,120 alleles · very rare exomes 14/1,461,882 · genomes 2/152,238 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,547
European (non-Finnish)	0.00119%	84,289

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.Pro197=
Coding: c.591C>T
MANE Select: NM_016203
dbSNP: rs587781126
Type: single nucleotide variant
Location: chr7:151675513 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 197: the 'disordered' region

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 lethal congenital glycogen storage disease of heart

Similar variants

PRKAG2 p.Pro197Arg Uncertain significance ★★ ⚠ same residue
PRKAG2 p.Pro197Leu Uncertain significance ★★ ⚠ same residue
PRKAG2 p.Pro197Ser Uncertain significance ★ ⚠ same residue
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

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-pro197 (accessed [today's date]).

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