Is AKT3 p.Pro448Ser (c.1342C>T) pathogenic?

AKT3 p.Pro448Ser (c.1342C>T) is classified Likely pathogenic in AKT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-15). AlphaMissense: likely pathogenic (0.9653); Absent from gnomAD v4.1; Associated with AKT3-related disorder.

What condition is associated with AKT3 p.Pro448Ser (c.1342C>T)?

AKT3 p.Pro448Ser (c.1342C>T) is associated with AKT3-related disorder (ClinVar).

How common is AKT3 p.Pro448Ser (c.1342C>T) in the general population?

AKT3 p.Pro448Ser (c.1342C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AKT3 p.Pro448Ser (c.1342C>T)?

AlphaMissense predicts likely pathogenic (score 0.9653) — an in-silico prediction, not a clinical call.

AKT3 p.Pro448Ser

c.1342C>T · VCV4950088

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

AKT3-related disorder

Computational evidence

Protein change
AlphaMissense	0.9653	likely pathogenic ✓ concordant with ClinVar
REVEL	0.51	indeterminate
SaProt	LLR -12.60	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 12	GERP 1.9, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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: AKT3
Protein: p.Pro448Ser
Coding: c.1342C>T
MANE Select: NM_005465
Type: single nucleotide variant
Location: chr1:243512336 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 82.42 · 2 PDB
Residue 448: the agc-kinase c-terminal domain

Full AKT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AKT3-related disorder

Similar variants

AKT3 p.Pro448= Likely benign same residue
AKT3 p.Pro448Thr Likely benign ★ same residue
AKT3 p.Asn229Ile Pathogenic/Likely pathogenic ★★ same condition
SDCCAG8 p.Thr703Ile Uncertain significance ★★ ⚠ same condition
AKT3 c.47-2A>G Likely pathogenic ★ same condition
AKT3 p.Asp322Ala Likely pathogenic ★ ⚠ same condition
AKT3 p.Gln60Ter Likely pathogenic ★ same condition
AKT3 p.Glu114Ter Pathogenic ★ 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/akt3-p-pro448ser (accessed [today's date]).

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