Is PRKAG2 p.Pro83= (c.249C>T) pathogenic?

PRKAG2 p.Pro83= (c.249C>T) is classified Likely benign in PRKAG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-09). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with PRKAG2 p.Pro83= (c.249C>T)?

PRKAG2 p.Pro83= (c.249C>T) is associated with Cardiovascular phenotype, cardiomyopathy, lethal congenital glycogen storage disease of heart (ClinVar).

How common is PRKAG2 p.Pro83= (c.249C>T) in the general population?

PRKAG2 p.Pro83= (c.249C>T) is absent from gnomAD v4.1 (gnomAD).

PRKAG2 p.Pro83=

c.249C>T · rs2537923268 · VCV1997894

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.6	GERP -3.4, phastCons 1
Overall
CADD	8.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKAG2
Protein: p.Pro83=
Coding: c.249C>T
MANE Select: NM_016203
dbSNP: rs2537923268
Type: single nucleotide variant
Location: chr7:151781369 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 83: 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 lethal congenital glycogen storage disease of heart

Similar variants

PRKAG2 p.Pro83Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PRKAG2 p.Pro83Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PRKAG2 p.Arg302Gln Pathogenic ★★ same condition
PRKAG2 p.Arg302Pro Pathogenic/Likely pathogenic ★★ same condition
PRKAG2 p.Arg531Gln Pathogenic ★★ same condition
PRKAG2 p.His530Arg Pathogenic ★★ same condition
PRKAG2 p.Phe293Leu Pathogenic/Likely pathogenic ★★ same condition
PRKAG2 c.1005+6T>C Uncertain significance ★★ 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-pro83 (accessed [today's date]).

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