Is PRKAG2 p.Val282Phe (c.844G>T) pathogenic?

PRKAG2 p.Val282Phe (c.844G>T) is classified Uncertain significance in PRKAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely pathogenic (0.9904); Absent from gnomAD v4.1; Associated with PRKAG2-related cardiomyopathy.

What condition is associated with PRKAG2 p.Val282Phe (c.844G>T)?

PRKAG2 p.Val282Phe (c.844G>T) is associated with PRKAG2-related cardiomyopathy (ClinVar).

How common is PRKAG2 p.Val282Phe (c.844G>T) in the general population?

PRKAG2 p.Val282Phe (c.844G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKAG2 p.Val282Phe (c.844G>T)?

AlphaMissense predicts likely pathogenic (score 0.9904) — an in-silico prediction, not a clinical call.

PRKAG2 p.Val282Phe

c.844G>T · VCV4532062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9904 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PRKAG2-related cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9904	likely pathogenic
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -14.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.46, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 38 kb · p 8.3e-20 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Val282Phe
Coding: c.844G>T
MANE Select: NM_016203
Type: single nucleotide variant
Location: chr7:151595365 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 282: the cbs 1 domain

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

Disease context

PRKAG2-related cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRKAG2 p.Val282= Likely benign ★ same residue
PRKAG2 p.Asp51Glu Uncertain significance ★★ ⚠ same condition
PRKAG2 p.Pro118Ser Uncertain significance ★★ ⚠ same condition
PRKAG2 p.Asn325Asp Uncertain significance ★ ⚠ same condition
PRKAG2 p.Val289Asp Uncertain significance ★ ⚠ same condition
PRKAG2 p.Arg302Gln Pathogenic ★★ same type
PRKAG2 p.Arg302Pro Pathogenic/Likely pathogenic ★★ same type
PRKAG2 p.Arg531Gln Pathogenic ★★ same type

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-val282phe (accessed [today's date]).

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