Is PRKAG2 p.Arg34= (c.102C>G) pathogenic?

PRKAG2 p.Arg34= (c.102C>G) is classified Likely benign in PRKAG2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-12). Very rare (popmax 8.48e-05%, nfe); Associated with cardiomyopathy.

What condition is associated with PRKAG2 p.Arg34= (c.102C>G)?

PRKAG2 p.Arg34= (c.102C>G) is associated with cardiomyopathy, hypertrophic cardiomyopathy, lethal congenital glycogen storage disease of heart (ClinVar).

How common is PRKAG2 p.Arg34= (c.102C>G) in the general population?

PRKAG2 p.Arg34= (c.102C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PRKAG2 p.Arg34=

c.102C>G · rs1057522970 · VCV387985

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

cardiomyopathy

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 -3.4, phastCons 0.001
Overall
CADD	9.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,762 alleles

Overall 6.22e-05% 1/1,606,916 alleles · very rare exomes 1/1,454,672 · genomes 0/152,244 · 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.Arg34=
Coding: c.102C>G
MANE Select: NM_016203
dbSNP: rs1057522970
Type: single nucleotide variant
Location: chr7:151876519 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 34: 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.Arg34Cys 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-arg34 (accessed [today's date]).

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