Is PRKAG2 p.Pro83Ser (c.247C>T) pathogenic?

PRKAG2 p.Pro83Ser (c.247C>T) is classified Conflicting classifications of pathogenicity in PRKAG2 (ClinVar, Conflicting submitters, 16 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0673); Rare (popmax 0.248%, mid); Associated with Cardiovascular phenotype.

What condition is associated with PRKAG2 p.Pro83Ser (c.247C>T)?

PRKAG2 p.Pro83Ser (c.247C>T) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is PRKAG2 p.Pro83Ser (c.247C>T) in the general population?

PRKAG2 p.Pro83Ser (c.247C>T) is rare (popmax 0.248%, mid) (gnomAD).

What do computational predictors say about PRKAG2 p.Pro83Ser (c.247C>T)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

PRKAG2 p.Pro83Ser

c.247C>T · rs148791216 · VCV45711

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.248%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -3.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -3.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 281 kb · p 0.8 · regional, not allelic
Overall
CADD	11.68	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.248% Middle Eastern · 15/6,038 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0327% 528/1,613,136 alleles · rare exomes 473/1,460,826 · genomes 55/152,310 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.248%	403
South Asian	0.133%	752
Remaining individualsnot grpmax-eligible	0.0608%	1,643
Admixed American	0.0384%	2,605
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,958
European (non-Finnish)	0.0267%	3,745
African / African-American	0.00666%	15,008
East Asian	0.00223%	44,852

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.Pro83Ser
Coding: c.247C>T
MANE Select: NM_016203
dbSNP: rs148791216
Type: single nucleotide variant
Location: chr7:151781371 (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 hypertrophic cardiomyopathy heart failure Wolff-Parkinson-White syndrome lethal congenital glycogen storage disease of heart hypertrophic cardiomyopathy 6

Similar variants

PRKAG2 p.Pro83= Likely benign ★★ same residue
PRKAG2 p.Pro83Leu 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.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-pro83ser (accessed [today's date]).

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