Is PTEN p.Tyr178Phe (c.533A>T) pathogenic?

PTEN p.Tyr178Phe (c.533A>T) is classified Uncertain significance in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). AlphaMissense: ambiguous (0.398); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Tyr178Phe (c.533A>T)?

PTEN p.Tyr178Phe (c.533A>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Tyr178Phe (c.533A>T) in the general population?

PTEN p.Tyr178Phe (c.533A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTEN p.Tyr178Phe (c.533A>T)?

AlphaMissense predicts ambiguous (score 0.398) — an in-silico prediction, not a clinical call.

PTEN p.Tyr178Phe

c.533A>T · rs786204866 · VCV1746919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.398 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.398	ambiguous
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -8.84	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 32 kb · p 4.1e-17 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Tyr178Phe
Coding: c.533A>T
MANE Select: NM_000314
dbSNP: rs786204866
Type: single nucleotide variant
Location: chr10:87952158 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTEN p.Tyr178= Benign/Likely benign ★★ same residue
PTEN p.Tyr178Asn Likely pathogenic ★ same residue
PTEN p.Tyr178del Likely pathogenic ★★★ same residue
PTEN p.Tyr178Ter Pathogenic ★ 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 c.1026+1G>A 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-tyr178phe (accessed [today's date]).

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