Is PTEN p.Glu99fs (c.296_297insTA) pathogenic?

PTEN p.Glu99fs (c.296297insTA) is classified Likely pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Absent from gnomAD; Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Glu99fs (c.296_297insTA)?

PTEN p.Glu99fs (c.296_297insTA) is associated with Cowden syndrome 1 (ClinVar).

How common is PTEN p.Glu99fs (c.296_297insTA) in the general population?

PTEN p.Glu99fs (c.296_297insTA) is absent from gnomAD (gnomAD).

PTEN p.Glu99fs

c.296_297insTA · rs2493716509 · VCV1723126

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 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	predicted	premature termination codon in exon 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.3, 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.Glu99fs
Coding: c.296_297insTA
MANE Select: NM_000314
dbSNP: rs2493716509
Type: Insertion
Location: chr10:87933054 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 99: an α-helix; the phosphatase 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

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

Similar variants

PTEN p.Leu247fs Pathogenic/Likely pathogenic ★★ same condition
PTEN c.802-14_802-13insC Likely benign ★★ same condition
PTEN c.802-8_802-7insC Likely benign ★★ same condition
PTEN c.802-9_802-8insC Likely benign ★★ same condition
PTEN p.Gln245fs Pathogenic ★ same condition
PTEN p.Leu247Ter Pathogenic ★ same condition
PTEN p.Lys183Ter Pathogenic ★ same condition
PTEN p.Pro30fs 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-glu99fs (accessed [today's date]).

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