Is PRKAG2 p.Ser196Pro (c.586T>C) pathogenic?

PRKAG2 p.Ser196Pro (c.586T>C) is classified Uncertain significance in PRKAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-10). AlphaMissense: likely benign (0.0936); Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy.

What condition is associated with PRKAG2 p.Ser196Pro (c.586T>C)?

PRKAG2 p.Ser196Pro (c.586T>C) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is PRKAG2 p.Ser196Pro (c.586T>C) in the general population?

PRKAG2 p.Ser196Pro (c.586T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKAG2 p.Ser196Pro (c.586T>C)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

PRKAG2 p.Ser196Pro

c.586T>C · rs1585680609 · VCV3070351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -6.12	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 4.3	GERP -0.63, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 281 kb · p 0.8 · regional, not allelic
Overall
CADD	19.32	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

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.Ser196Pro
Coding: c.586T>C
MANE Select: NM_016203
dbSNP: rs1585680609
Type: single nucleotide variant
Location: chr7:151675518 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 196: the 'disordered' region; a modified residue (phosphoserine)

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

Disease context

hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRKAG2 p.Ser196Phe Uncertain significance ★★ ⚠ same residue
PRKAG2 p.Ser196= Likely benign ★★ same residue
PRKAG2 p.Arg302Gln 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-ser196pro (accessed [today's date]).

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