Is PTEN p.Phe279fs (c.836del) pathogenic?

PTEN p.Phe279fs (c.836del) is classified Pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Phe279fs (c.836del)?

PTEN p.Phe279fs (c.836del) is associated with PTEN hamartoma tumor syndrome (ClinVar).

How is PTEN hamartoma tumor syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PTEN p.Phe279fs

c.836del · VCV4974549

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

PTEN hamartoma tumor syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PTEN
Protein: p.Phe279fs
Coding: c.836del
MANE Select: NM_000314
Type: Deletion
Location: chr10:87960927 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 279: an α-helix; the c2 tensin-type domain; a UniProt-annotated variant site (in mcephas)

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

Disease context

PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PTEN hamartoma tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

PTEN p.Phe279_Pro283del Uncertain significance ★ same residue
PTEN p.Phe279Leu Uncertain significance ★★ ⚠ same residue
PTEN p.Phe279= Benign/Likely benign ★★ same residue
PTEN c.209+4_209+7del Pathogenic ★★★ same condition
PTEN c.210-2_211del Pathogenic ★★★ same condition
PTEN c.801+1del Pathogenic ★★★ same condition
PTEN c.802-2del Pathogenic ★★★ same condition
PTEN p.Asn329fs 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/pten-p-phe279fs (accessed [today's date]).

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