Is PTEN p.Tyr178Ter (c.534T>G) pathogenic?

PTEN p.Tyr178Ter (c.534T>G) is classified Pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Absent from gnomAD v4.1; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Tyr178Ter (c.534T>G)?

PTEN p.Tyr178Ter (c.534T>G) is associated with PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Tyr178Ter (c.534T>G) in the general population?

PTEN p.Tyr178Ter (c.534T>G) is absent from gnomAD v4.1 (gnomAD).

How is PTEN hamartoma tumor syndrome inherited?

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

PTEN p.Tyr178Ter

c.534T>G · VCV4056257

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PTEN hamartoma tumor syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.28, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTEN
Protein: p.Tyr178Ter
Coding: c.534T>G
MANE Select: NM_000314
Type: single nucleotide variant
Location: chr10:87952159 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 178: 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

PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PTEN hamartoma tumor syndrome (Orphanet):

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

Similar variants

PTEN p.Tyr178= Benign/Likely benign ★★ same residue
PTEN p.Tyr178Asp Uncertain significance ★ ⚠ same residue
PTEN p.Tyr178Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Tyr178His Uncertain significance ★ ⚠ same residue
PTEN p.Tyr178_Ser179delinsTer Pathogenic ★★★ same residue
PTEN p.Tyr178del Likely pathogenic ★★★ same residue
PTEN p.Tyr178Asn Likely pathogenic ★ same residue
PTEN p.Tyr178Phe Uncertain significance ★ ⚠ same residue

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-tyr178ter (accessed [today's date]).

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