Is PTEN p.Glu43fs (c.127dup) pathogenic?

PTEN p.Glu43fs (c.127dup) is classified Pathogenic in PTEN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-20). Absent from gnomAD; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Glu43fs (c.127dup)?

PTEN p.Glu43fs (c.127dup) is associated with PTEN hamartoma tumor syndrome, hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Glu43fs (c.127dup) in the general population?

PTEN p.Glu43fs (c.127dup) is absent from gnomAD (gnomAD).

How is PTEN hamartoma tumor syndrome inherited?

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

PTEN p.Glu43fs

c.127dup · rs1554893810 · VCV482077

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, 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.Glu43fs
Coding: c.127dup
MANE Select: NM_000314
dbSNP: rs1554893810
Type: Duplication
Location: chr10:87894071 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 43: the phosphatase tensin-type domain

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

Also linked: hereditary neoplastic syndrome

For PTEN hamartoma tumor syndrome (Orphanet):

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

Similar variants

PTEN p.Glu43Ter Pathogenic ★★ same residue
PTEN p.Glu43= Benign/Likely benign ★★ same residue
PTEN p.Glu43Ala Uncertain significance ★ ⚠ same residue
PTEN p.Glu43Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Arg172fs Pathogenic ★★★ same condition
PTEN c.209+2dup Uncertain significance ★★★ same condition
PTEN p.Lys102dup Uncertain significance ★★★ same condition
PTEN c.254-30dup Benign ★★★ 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-glu43fs (accessed [today's date]).

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