Is PTEN p.Glu373fs (c.1116_1119del) pathogenic?

PTEN p.Glu373fs (c.11161119del) is classified Pathogenic/Likely pathogenic in PTEN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-04). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Glu373fs (c.1116_1119del)?

PTEN p.Glu373fs (c.1116_1119del) is associated with hereditary neoplastic syndrome, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Glu373fs (c.1116_1119del) in the general population?

PTEN p.Glu373fs (c.1116_1119del) is absent from gnomAD (gnomAD).

PTEN p.Glu373fs

c.1116_1119del · rs1554826049 · VCV484597

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely 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

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	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 7.7	GERP 2.9, 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.

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.Glu373fs
Coding: c.1116_1119del
MANE Select: NM_000314
dbSNP: rs1554826049
Type: Deletion
Location: chr10:87965374 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 373: a UniProt-annotated variant site (in mcephas); the 'disordered' region

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: PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Glu373= Likely benign ★★ 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 c.802-2del Pathogenic ★★★ same condition
PTEN p.Asn329fs Pathogenic ★★★ same condition
PTEN p.Gln17fs Pathogenic ★★★ same condition
PTEN p.Tyr76del 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-glu373fs (accessed [today's date]).

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