Is AKT2 p.Pro370= (c.1110G>T) pathogenic?

AKT2 p.Pro370= (c.1110G>T) is classified Benign/Likely benign in AKT2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-19). Rare (popmax 0.254%, nfe); Associated with hypoinsulinemic hypoglycemia and body hemihypertrophy.

How common is AKT2 p.Pro370= (c.1110G>T) in the general population?

AKT2 p.Pro370= (c.1110G>T) is rare (popmax 0.254%, nfe) (gnomAD).

AKT2 p.Pro370=

Q: What condition is associated with AKT2 p.Pro370= (c.1110G>T)?

AKT2 p.Pro370= (c.1110G>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.1110G>T · rs41309435 · VCV466265

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.254%, 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 -20	GERP -4.5
Overall
CADD	0.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.254% European (non-Finnish) · 2,993/1,180,014 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.243%

Overall 0.284% 4,577/1,613,886 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.16%	46
European (non-Finnish)grpmax	0.254%	394
Remaining individualsnot grpmax-eligible	0.208%	481
Admixed American	0.0683%	1,464
African / African-American	0.0427%	2,344
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401

Finnish 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.Pro370=
Coding: c.1110G>T
MANE Select: NM_001626
dbSNP: rs41309435
Type: single nucleotide variant
Location: chr19:40235955 (GRCh38)
Gene constraint: LOEUF 0.398 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 82.79 · 19 PDB
Residue 370: 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-pro370 (accessed [today's date]).

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