Is AKT1 p.Pro451= (c.1353A>G) pathogenic?

AKT1 p.Pro451= (c.1353A>G) is classified Likely benign in AKT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AKT1 p.Pro451= (c.1353A>G)?

AKT1 p.Pro451= (c.1353A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AKT1 p.Pro451= (c.1353A>G) in the general population?

AKT1 p.Pro451= (c.1353A>G) is absent from gnomAD v4.1 (gnomAD).

AKT1 p.Pro451=

c.1353A>G · rs1595239033 · VCV2587633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

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 -3.9
Overall
CADD	5.529	PHRED · no single calibrated threshold — expert panels disagree

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: AKT1
Protein: p.Pro451=
Coding: c.1353A>G
MANE Select: NM_001382430
dbSNP: rs1595239033
Type: single nucleotide variant
Location: chr14:104770755 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.62 · 55 PDB
Residue 451: the agc-kinase c-terminal domain; the 'disordered' region

Full AKT1 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

AKT1 p.Pro451Ala Uncertain significance ★ ⚠ same residue
AKT1 p.Pro451Ser Uncertain significance ★ ⚠ same residue
AKT1 p.Arg346Cys Uncertain significance ★★ ⚠ same condition
AKT1 p.Asn128Ile Uncertain significance ★★ ⚠ same condition
AKT1 p.Asn324Ser Uncertain significance ★★ ⚠ same condition
AKT1 p.Asn351Ser Uncertain significance ★★ ⚠ same condition
AKT1 p.Asp119Gly Uncertain significance ★★ ⚠ same condition
AKT1 p.Glu117Asp 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/akt1-p-pro451 (accessed [today's date]).

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