Is PTEN p.Val53Asp (c.158_159delinsAT) pathogenic?

PTEN p.Val53Asp (c.158159delinsAT) is classified Uncertain significance in PTEN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). Absent from gnomAD; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Val53Asp (c.158_159delinsAT)?

PTEN p.Val53Asp (c.158_159delinsAT) is associated with PTEN hamartoma tumor syndrome, hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Val53Asp (c.158_159delinsAT) in the general population?

PTEN p.Val53Asp (c.158_159delinsAT) 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.Val53Asp

c.158_159delinsAT · rs2132187834 · VCV1052224

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic

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.Val53Asp
Coding: c.158_159delinsAT
MANE Select: NM_000314
dbSNP: rs2132187834
Type: Indel
Location: chr10:87894103 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 53: an α-helix; 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.Val53Ile Pathogenic ★★★ same residue
PTEN p.Val53= Likely benign ★★★ same residue
PTEN p.Val53Glu Uncertain significance ★★ ⚠ same residue
PTEN p.Val53Gly Uncertain significance ★ ⚠ same residue
PTEN p.Val53fs Pathogenic ★ same residue
PTEN p.Tyr178_Ser179delinsTer Pathogenic ★★★ same condition
PTEN c.156_164+4delinsCAT Likely pathogenic ★★ same condition
PTEN p.Asp326_Lys330delinsAlaTer Pathogenic/Likely 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-val53asp (accessed [today's date]).

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