Is AKT1 p.Phe293= (c.879C>T) pathogenic?

AKT1 p.Phe293= (c.879C>T) is classified Likely benign in AKT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-06). Very rare (popmax 0.00933%, afr); Associated with Cowden syndrome 6.

What condition is associated with AKT1 p.Phe293= (c.879C>T)?

AKT1 p.Phe293= (c.879C>T) is associated with Cowden syndrome 6 (ClinVar).

How common is AKT1 p.Phe293= (c.879C>T) in the general population?

AKT1 p.Phe293= (c.879C>T) is very rare (popmax 0.00933%, afr) (gnomAD).

AKT1 p.Phe293=

c.879C>T · rs139200289 · VCV416464

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00933%, afr)

Conditions

Cowden syndrome 6

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 -5.5	GERP -4.2
Overall
CADD	10.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00933% African / African-American · 7/75,052 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.00167% 27/1,614,184 alleles · very rare exomes 17/1,461,860 · genomes 10/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,722
Remaining individualsnot grpmax-eligible	0.0064%	15,628
Finnishnot grpmax-eligible	0.00468%	21,348
East Asian	0.00223%	44,886
South Asian	0.0011%	91,092
European (non-Finnish)	0.000932%	107,272

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.Phe293=
Coding: c.879C>T
MANE Select: NM_001382430
dbSNP: rs139200289
Type: single nucleotide variant
Location: chr14:104773329 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.62 · 55 PDB
Residue 293: the protein kinase domain

Full AKT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cowden syndrome 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AKT1 p.Glu17Lys Pathogenic ★★ same condition
AKT1 c.1260+5G>A Uncertain significance ★★ same condition
AKT1 c.176-3C>T Uncertain significance ★★ same condition
AKT1 c.176-5C>A Uncertain significance ★★ same condition
AKT1 c.288-3C>T Uncertain significance ★★ same condition
AKT1 p.Ala139Pro Uncertain significance ★★ ⚠ same condition
AKT1 p.Ala171Thr Uncertain significance ★★ ⚠ same condition
AKT1 p.Ala212Gly 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-phe293 (accessed [today's date]).

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