Is PTEN p.Arg130fs (c.389del) pathogenic?

PTEN p.Arg130fs (c.389del) is classified Pathogenic in PTEN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-09-27). Absent from gnomAD; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Arg130fs (c.389del)?

PTEN p.Arg130fs (c.389del) is associated with PTEN hamartoma tumor syndrome, Cowden syndrome 1 (ClinVar).

How common is PTEN p.Arg130fs (c.389del) in the general population?

PTEN p.Arg130fs (c.389del) 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.Arg130fs

c.389del · rs121913292 · VCV192224

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 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 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	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.Arg130fs
Coding: c.389del
MANE Select: NM_000314
dbSNP: rs121913292
Type: Deletion
Location: chr10:87933148 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 130: an α-helix; the phosphatase tensin-type domain; a UniProt-annotated variant site (in mcephas); a UniProt-annotated variant site (in cws1; loss of phosphatase activity towards ins(1,3,4,5)p4 and ptdins(3,4,5)p3); a UniProt-annotated variant site (in cws1; also found in endometrial hyperplasia; loss of phosphatase activity towards ins(1,3,4,5)p4; retains ability to bind phospholipid membranes); a UniProt-annotated variant site (in cws1; loss of phosphatase activity towards ins(1,3,4,5)p4; retains ability to bind phospholipid membranes)

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: Cowden syndrome 1

For PTEN hamartoma tumor syndrome (Orphanet):

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

Similar variants

PTEN p.Arg130Gln Pathogenic ★★★ same residue
PTEN p.Arg130Gly Pathogenic ★★★ same residue
PTEN p.Arg130Pro Pathogenic ★★★ same residue
PTEN p.Arg130Leu Pathogenic/Likely pathogenic ★★ same residue
PTEN p.Arg130Ter Pathogenic ★★ same residue
PTEN p.Arg130= Likely benign ★ same residue
PTEN c.209+4_209+7del Pathogenic ★★★ same condition
PTEN c.210-2_211del 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-arg130fs (accessed [today's date]).

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