Is PRKAG2 p.Asp49= (c.147C>T) pathogenic?

PRKAG2 p.Asp49= (c.147C>T) is classified Likely benign in PRKAG2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2025-10-27). Very rare (popmax 0.00994%, sas); Associated with lethal congenital glycogen storage disease of heart.

What condition is associated with PRKAG2 p.Asp49= (c.147C>T)?

PRKAG2 p.Asp49= (c.147C>T) is associated with lethal congenital glycogen storage disease of heart, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is PRKAG2 p.Asp49= (c.147C>T) in the general population?

PRKAG2 p.Asp49= (c.147C>T) is very rare (popmax 0.00994%, sas) (gnomAD).

PRKAG2 p.Asp49=

Q: How is Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

c.147C>T · rs761196275 · VCV696154

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00994%, sas)

Conditions

lethal congenital glycogen storage disease of heart

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 -0.055	GERP -3.1, phastCons 0.025
Overall
CADD	9.193	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00994% South Asian · 9/90,568 alleles

Filtering AF 0.00516% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00377%

Overall 0.00403% 65/1,612,884 alleles · very rare exomes 60/1,460,656 · genomes 5/152,228 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00994%	10,063
European (non-Finnish)	0.00415%	24,075
Admixed American	0.00334%	29,935
Remaining individualsnot grpmax-eligible	0.0032%	31,229
East Asian	0.00223%	44,880
Finnishnot grpmax-eligible	0.00156%	63,964
African / African-American	0.00133%	74,916

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.Asp49=
Coding: c.147C>T
MANE Select: NM_016203
dbSNP: rs761196275
Type: single nucleotide variant
Location: chr7:151786509 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 49: the 'disordered' region

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

Disease context

lethal congenital glycogen storage disease of heart — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy Wolff-Parkinson-White syndrome hypertrophic cardiomyopathy 6

For Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease (Orphanet):

Inheritance: Not applicable
Onset: Antenatal, Neonatal

Similar variants

PRKAG2 p.Asp49Asn Uncertain significance ★ ⚠ same residue
PRKAG2 p.Asp49Glu 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

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-asp49 (accessed [today's date]).

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