Is PTEN p.Phe341fs (c.1023del) pathogenic?

PTEN p.Phe341fs (c.1023del) is classified Likely pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-25). Absent from gnomAD; Associated with Cowden disease.

What condition is associated with PTEN p.Phe341fs (c.1023del)?

PTEN p.Phe341fs (c.1023del) is associated with Cowden disease (ClinVar).

How common is PTEN p.Phe341fs (c.1023del) in the general population?

PTEN p.Phe341fs (c.1023del) is absent from gnomAD (gnomAD).

PTEN p.Phe341fs

c.1023del · rs1564568689 · VCV623215

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cowden disease

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 within the last 50 nt of the penultimate exon (8 of 9, 6 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PTEN
Protein: p.Phe341fs
Coding: c.1023del
MANE Select: NM_000314
dbSNP: rs1564568689
Type: Deletion
Location: chr10:87961112 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 341: a UniProt-annotated variant site (in cws1; loss of interaction with nop53; decreased phosphorylation at s-380; decreased stability; loss of phosphatase activity towards ins(1,3,4,5)p4); 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 disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTEN p.Phe341Val Uncertain significance ★★★ ⚠ same residue
PTEN p.Arg142fs Pathogenic ★★ same condition
PTEN p.Ser170fs Pathogenic ★★ same condition
PTEN p.Phe56_Leu57insTer Pathogenic ★ same condition
PTEN p.Phe341Cys Uncertain significance ★ ⚠ same residue
PTEN p.Phe341Ile Uncertain significance ★ ⚠ same residue
PTEN c.165-1G>C Pathogenic ★★★ same condition
PTEN p.Arg130Gln 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-phe341fs (accessed [today's date]).

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