Is AKT2 p.Lys285= (c.855A>G) pathogenic?

AKT2 p.Lys285= (c.855A>G) is classified Likely benign in AKT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). Very rare (popmax 8.47e-05%, nfe); Associated with hypoinsulinemic hypoglycemia and body hemihypertrophy.

How common is AKT2 p.Lys285= (c.855A>G) in the general population?

AKT2 p.Lys285= (c.855A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

AKT2 p.Lys285=

Q: What condition is associated with AKT2 p.Lys285= (c.855A>G)?

AKT2 p.Lys285= (c.855A>G) is associated with hypoinsulinemic hypoglycemia and body hemihypertrophy, type 2 diabetes mellitus (ClinVar).

Q: How is Hypoinsulinemic hypoglycemia and body hemihypertrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.855A>G · VCV3753542

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hypoinsulinemic hypoglycemia and body hemihypertrophy

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 1.2	GERP 0.15, phastCons 1
Overall
CADD	9.747	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,830 alleles · very rare

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: AKT2
Protein: p.Lys285=
Coding: c.855A>G
MANE Select: NM_001626
Type: single nucleotide variant
Location: chr19:40236362 (GRCh38)
Gene constraint: LOEUF 0.398 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 82.79 · 19 PDB
Residue 285: the protein kinase domain

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

Disease context

hypoinsulinemic hypoglycemia and body hemihypertrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus

For Hypoinsulinemic hypoglycemia and body hemihypertrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

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-lys285 (accessed [today's date]).

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