Is AKT2 p.Asp94= (c.282C>T) pathogenic?

AKT2 p.Asp94= (c.282C>T) is classified Likely benign in AKT2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-14). Rare (popmax 0.822%, eas); Associated with hypoinsulinemic hypoglycemia and body hemihypertrophy.

How common is AKT2 p.Asp94= (c.282C>T) in the general population?

AKT2 p.Asp94= (c.282C>T) is rare (popmax 0.822%, eas) (gnomAD).

AKT2 p.Asp94=

Q: What condition is associated with AKT2 p.Asp94= (c.282C>T)?

AKT2 p.Asp94= (c.282C>T) 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.282C>T · rs139125633 · VCV466266

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.822%, eas)

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 -2.5	GERP -4.5
Overall
CADD	7.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.822% East Asian · 369/44,870 alleles

Filtering AF 0.753% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.726%

Overall 0.0666% 1,075/1,613,134 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.64%	61
East Asiangrpmax	0.822%	122
Remaining individualsnot grpmax-eligible	0.118%	844
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.0114%	8,734
South Asian	0.00769%	13,009
African / African-American	0.004%	25,005
Admixed American	0.00167%	60,006

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp94=
Coding: c.282C>T
MANE Select: NM_001626
dbSNP: rs139125633
Type: single nucleotide variant
Location: chr19:40255163 (GRCh38)
Gene constraint: LOEUF 0.398 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 82.79 · 19 PDB
Residue 94: the ph domain; an α-helix

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 p.Asp94Glu Uncertain significance ★ ⚠ same residue
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

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-asp94 (accessed [today's date]).

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