Is AKT1 p.Pro93= (c.279T>C) pathogenic?

AKT1 p.Pro93= (c.279T>C) is classified Likely benign in AKT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-15). Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AKT1 p.Pro93= (c.279T>C)?

AKT1 p.Pro93= (c.279T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AKT1 p.Pro93= (c.279T>C) in the general population?

AKT1 p.Pro93= (c.279T>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

AKT1 p.Pro93=

c.279T>C · VCV4574088

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

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 -14	GERP -4.2
Overall
CADD	0.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,680 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,966 alleles · very rare exomes 5/1,460,750 · genomes 1/152,216 · joint denominator

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: AKT1
Protein: p.Pro93=
Coding: c.279T>C
MANE Select: NM_001382430
Type: single nucleotide variant
Location: chr14:104776667 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.62 · 55 PDB
Residue 93: the ph domain; an α-helix

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.Pro93His 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
AKT1 p.Glu397Lys 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-pro93 (accessed [today's date]).

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