Is AKT2 p.Pro68Thr (c.202C>A) pathogenic?

AKT2 p.Pro68Thr (c.202C>A) is classified Uncertain significance in AKT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-13). AlphaMissense: likely pathogenic (0.9865); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AKT2 p.Pro68Thr (c.202C>A)?

AKT2 p.Pro68Thr (c.202C>A) is associated with Inborn genetic diseases (ClinVar).

How common is AKT2 p.Pro68Thr (c.202C>A) in the general population?

AKT2 p.Pro68Thr (c.202C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AKT2 p.Pro68Thr (c.202C>A)?

AlphaMissense predicts likely pathogenic (score 0.9865) — an in-silico prediction, not a clinical call.

AKT2 p.Pro68Thr

c.202C>A · rs2145293995 · VCV2472609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9865 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9865	likely pathogenic
REVEL	0.436	indeterminate
SaProt	LLR -11.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 27 kb · p 3.2e-08 · regional, not allelic
Overall
CADD	27.3	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: AKT2
Protein: p.Pro68Thr
Coding: c.202C>A
MANE Select: NM_001626
dbSNP: rs2145293995
Type: single nucleotide variant
Location: chr19:40255243 (GRCh38)
Gene constraint: LOEUF 0.398 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 82.79 · 19 PDB
Residue 68: the ph domain; a disulfide bond; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AKT2 p.Pro68= Conflicting classifications of pathogenicity ★ same residue
AKT2 p.Gln429Arg Uncertain significance ★★ ⚠ same condition
AKT2 p.Ala445Val Uncertain significance ★ ⚠ same condition
AKT2 p.Arg170Trp Uncertain significance ★ ⚠ same condition
AKT2 p.Arg245Cys Uncertain significance ★ ⚠ same condition
AKT2 p.Arg392Trp Uncertain significance ★ ⚠ same condition
AKT2 p.Asp192Gly Uncertain significance ★ ⚠ same condition
AKT2 p.Asp284His 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-pro68thr (accessed [today's date]).

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