Is PRKAG2 p.Phe43= (c.129C>T) pathogenic?

PRKAG2 p.Phe43= (c.129C>T) is classified Likely benign in PRKAG2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-01-19). Very rare (popmax 0.00446%, eas); Associated with cardiomyopathy.

What condition is associated with PRKAG2 p.Phe43= (c.129C>T)?

PRKAG2 p.Phe43= (c.129C>T) is associated with cardiomyopathy, hypertrophic cardiomyopathy, lethal congenital glycogen storage disease of heart (ClinVar).

How common is PRKAG2 p.Phe43= (c.129C>T) in the general population?

PRKAG2 p.Phe43= (c.129C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

PRKAG2 p.Phe43=

c.129C>T · rs770946241 · VCV924606

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

cardiomyopathy

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 0.31	GERP 1, phastCons 0.74
Overall
CADD	8.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000496% 8/1,612,698 alleles · very rare exomes 5/1,460,474 · genomes 3/152,224 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,440
Finnishnot grpmax-eligible	0.00156%	63,948
African / African-American	0.00133%	74,930
European (non-Finnish)	0.000339%	294,890

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.Phe43=
Coding: c.129C>T
MANE Select: NM_016203
dbSNP: rs770946241
Type: single nucleotide variant
Location: chr7:151786527 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 43: the 'disordered' region

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

Disease context

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

Also linked: hypertrophic cardiomyopathy lethal congenital glycogen storage disease of heart

Similar variants

PRKAG2 p.Phe43Leu 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
PRKAG2 p.Phe293Leu Pathogenic/Likely pathogenic ★★ same condition
PRKAG2 p.Thr400Asn Likely 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-phe43 (accessed [today's date]).

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