Is PTEN p.Thr319fs (c.955dup) pathogenic?

PTEN p.Thr319fs (c.955dup) is classified Pathogenic in PTEN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-30). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Thr319fs (c.955dup)?

PTEN p.Thr319fs (c.955dup) is associated with hereditary neoplastic syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Thr319fs (c.955dup) in the general population?

PTEN p.Thr319fs (c.955dup) is absent from gnomAD (gnomAD).

PTEN p.Thr319fs

c.955dup · rs786204892 · VCV189440

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic 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 0.41	GERP -3.8, 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.Thr319fs
Coding: c.955dup
MANE Select: NM_000314
dbSNP: rs786204892
Type: Duplication
Location: chr10:87961046 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 319: a modified residue (phosphothreonine); a β-strand; the c2 tensin-type domain; a UniProt-annotated variant site (in mcephas); a UniProt-annotated variant site (in glioma; reduced tumor suppressor activity; fails to inactivate akt/pkb)

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

Disease context

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

Also linked: Cowden syndrome 1 PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Thr319Asn Uncertain significance ★★ ⚠ same residue
PTEN p.Thr319_Leu320insTer Pathogenic ★ same residue
PTEN p.Thr319delinsIleTer Pathogenic ★ same residue
PTEN p.Thr319Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Thr319Ser Uncertain significance ★ ⚠ same residue
PTEN p.Thr319= Likely benign ★ same residue
PTEN p.Arg172fs Pathogenic ★★★ same condition
PTEN c.209+2dup 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-thr319fs (accessed [today's date]).

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