Is PTEN p.Leu57= (c.169T>C) pathogenic?

PTEN p.Leu57= (c.169T>C) is classified Benign in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). Absent from gnomAD v4.1; Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Leu57= (c.169T>C)?

PTEN p.Leu57= (c.169T>C) is associated with Cowden syndrome 1 (ClinVar).

How common is PTEN p.Leu57= (c.169T>C) in the general population?

PTEN p.Leu57= (c.169T>C) is absent from gnomAD v4.1 (gnomAD).

PTEN p.Leu57=

c.169T>C · VCV3903443

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,590,258)

Conditions

Cowden syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Overall
CADD	13.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,590,258). 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.Leu57=
Coding: c.169T>C
MANE Select: NM_000314
Type: single nucleotide variant
Location: chr10:87925517 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 57: an α-helix; the phosphatase tensin-type domain; a UniProt-annotated variant site (in glioma; likely pathogenic; loss of protein phosphatase activity)

Full PTEN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cowden syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTEN p.Leu57Trp Likely pathogenic ★★★ same residue
PTEN p.Leu57fs Pathogenic ★★ same residue
PTEN p.Leu57Val Uncertain significance ★★ ⚠ same residue
PTEN p.Leu57Ter Pathogenic ★ same residue
PTEN p.Leu57Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN c.1026+1G>A Pathogenic ★★★ same condition
PTEN c.1027-1G>A Pathogenic ★★★ same condition
PTEN c.165-1G>A 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-leu57 (accessed [today's date]).

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