Is AKT2 p.Arg437= (c.1311G>A) pathogenic?

AKT2 p.Arg437= (c.1311G>A) is classified Likely benign in AKT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-02). Absent from gnomAD v4.1; Associated with type 2 diabetes mellitus.

What condition is associated with AKT2 p.Arg437= (c.1311G>A)?

AKT2 p.Arg437= (c.1311G>A) is associated with type 2 diabetes mellitus, hypoinsulinemic hypoglycemia and body hemihypertrophy (ClinVar).

How common is AKT2 p.Arg437= (c.1311G>A) in the general population?

AKT2 p.Arg437= (c.1311G>A) is absent from gnomAD v4.1 (gnomAD).

AKT2 p.Arg437=

c.1311G>A · rs1973933516 · VCV2953395

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

type 2 diabetes mellitus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.65	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Overall
CADD	19.4	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: AKT2
Protein: p.Arg437=
Coding: c.1311G>A
MANE Select: NM_001626
dbSNP: rs1973933516
Type: single nucleotide variant
Location: chr19:40235100 (GRCh38)
Gene constraint: LOEUF 0.398 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 82.79 · 19 PDB
Residue 437: the agc-kinase c-terminal domain; an α-helix

Full AKT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

type 2 diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypoinsulinemic hypoglycemia and body hemihypertrophy

Similar variants

AKT2 c.709-3C>G Uncertain significance ★★ same condition
AKT2 c.960+3G>T Uncertain significance ★★ same condition
AKT2 p.Ala214Val Uncertain significance ★★ ⚠ same condition
AKT2 p.Arg113Trp Uncertain significance ★★ ⚠ same condition
AKT2 p.Arg15His Uncertain significance ★★ ⚠ same condition
AKT2 p.Arg253Gln Uncertain significance ★★ ⚠ same condition
AKT2 p.Arg347Cys Uncertain significance ★★ ⚠ same condition
AKT2 p.Asp399Asn 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/akt2-p-arg437 (accessed [today's date]).

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