Is PRKAG2 p.Asp372= (c.1116T>C) pathogenic?

PRKAG2 p.Asp372= (c.1116T>C) is classified Likely benign in PRKAG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-14). Very rare (popmax 0.00267%, afr); Associated with lethal congenital glycogen storage disease of heart.

How common is PRKAG2 p.Asp372= (c.1116T>C) in the general population?

PRKAG2 p.Asp372= (c.1116T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

PRKAG2 p.Asp372=

Q: What condition is associated with PRKAG2 p.Asp372= (c.1116T>C)?

PRKAG2 p.Asp372= (c.1116T>C) is associated with lethal congenital glycogen storage disease of heart, hypertrophic cardiomyopathy (ClinVar).

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.1116T>C · rs1359495243 · VCV520325

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 0.68	GERP 1.5, phastCons 0.93
Overall
CADD	7.507	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,942 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,808 alleles · very rare exomes 0/1,461,564 · genomes 2/152,244 · joint denominator

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.Asp372=
Coding: c.1116T>C
MANE Select: NM_016203
dbSNP: rs1359495243
Type: single nucleotide variant
Location: chr7:151568833 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 372: the cbs 2 domain

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: hypertrophic cardiomyopathy

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

Inheritance: Not applicable
Onset: Antenatal, Neonatal

Similar variants

PRKAG2 p.Asp372Asn Uncertain significance ★★ ⚠ same residue
PRKAG2 p.Asp372His 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-asp372 (accessed [today's date]).

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