Is PTEN p.Phe90Leu (c.270T>A) pathogenic?

PTEN p.Phe90Leu (c.270T>A) is classified Likely pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-06). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with PTEN p.Phe90Leu (c.270T>A)?

PTEN p.Phe90Leu (c.270T>A) is associated with hereditary breast carcinoma (ClinVar).

How common is PTEN p.Phe90Leu (c.270T>A) in the general population?

PTEN p.Phe90Leu (c.270T>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

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

What do computational predictors say about PTEN p.Phe90Leu (c.270T>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

PTEN p.Phe90Leu

c.270T>A · VCV4819386

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 8% in PTEN
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -12.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.23, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	27.6	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.Phe90Leu
Coding: c.270T>A
MANE Select: NM_000314
Type: single nucleotide variant
Location: chr10:87933029 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 90: a β-strand; 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 breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

PTEN p.Phe90Ser Pathogenic/Likely pathogenic ★★ same residue
PTEN p.Arg335Ter Pathogenic ★★★ same condition
PTEN p.Gln298Glu Likely benign ★★★ same condition
PTEN p.Phe90fs Pathogenic ★★ same residue
PTEN c.634+4A>G Likely pathogenic ★ same condition
PTEN c.210-7_210-3del Benign ★★★ same condition
PTEN c.1026+1G>A Pathogenic ★★★ same type
PTEN c.1027-1852A>G Likely pathogenic ★★★ same type

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-phe90leu (accessed [today's date]).

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