Is PRKAG2 p.Pro198= (c.594G>A) pathogenic?

PRKAG2 p.Pro198= (c.594G>A) is classified Benign/Likely benign in PRKAG2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0164%, mid); Associated with Cardiovascular phenotype.

What condition is associated with PRKAG2 p.Pro198= (c.594G>A)?

PRKAG2 p.Pro198= (c.594G>A) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is PRKAG2 p.Pro198= (c.594G>A) in the general population?

PRKAG2 p.Pro198= (c.594G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PRKAG2 p.Pro198=

c.594G>A · rs397517276 · VCV45726

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -4.7	GERP -3.2
Overall
CADD	10.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00316% 51/1,613,930 alleles · ultra-rare exomes 39/1,461,824 · genomes 12/152,106 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00446%	22,443
South Asian	0.00439%	22,770
African / African-American	0.00401%	24,968
European (non-Finnish)	0.00322%	31,053
Remaining individualsnot grpmax-eligible	0.0032%	31,242
Admixed American	0.00167%	59,988

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.Pro198=
Coding: c.594G>A
MANE Select: NM_016203
dbSNP: rs397517276
Type: single nucleotide variant
Location: chr7:151675510 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 198: 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.Pro198Ala Uncertain significance ★★ ⚠ same residue
PRKAG2 p.Pro198Leu Uncertain significance ★★ ⚠ same residue
PRKAG2 p.Pro198Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
PRKAG2 p.Pro198Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PRKAG2 p.Pro198fs Uncertain significance ★ same residue
PRKAG2 p.Arg302Gln Pathogenic ★★ same condition
PRKAG2 p.Arg302Pro Pathogenic/Likely pathogenic ★★ same condition
PRKAG2 p.Arg531Gln 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-pro198 (accessed [today's date]).

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