Is PTEN p.Phe347fs (c.1039_1043del) pathogenic?

PTEN p.Phe347fs (c.10391043del) is classified Likely pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-14). Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Phe347fs (c.1039_1043del)?

PTEN p.Phe347fs (c.1039_1043del) is associated with Cowden syndrome 1 (ClinVar).

PTEN p.Phe347fs

c.1039_1043del · VCV4852451

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cowden syndrome 1

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	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Variant & gene context

Gene: PTEN
Protein: p.Phe347fs
Coding: c.1039_1043del
MANE Select: NM_000314
Type: Deletion
Location: chr10:87965297 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 347: a UniProt-annotated variant site (in cws1; reduced phosphatase activity towards ins(1,3,4,5)p4); a β-strand; the c2 tensin-type domain; the 'required for interaction with nop53' region; a UniProt-annotated variant site (in mcephas)

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

Disease context

Cowden syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTEN p.Phe347= Benign/Likely benign ★★ same residue
PTEN p.Phe347del Uncertain significance ★ 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 p.Asn329fs Pathogenic ★★★ same condition
PTEN p.Gln17fs Pathogenic ★★★ same condition
PTEN c.*10del 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/pten-p-phe347fs (accessed [today's date]).

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