Is PTEN p.Leu70Phe (c.208C>T) pathogenic?

PTEN p.Leu70Phe (c.208C>T) is classified Uncertain significance in PTEN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-29). AlphaMissense: likely pathogenic (0.9945); Absent from gnomAD v4.1; Associated with glioma susceptibility 2.

What condition is associated with PTEN p.Leu70Phe (c.208C>T)?

PTEN p.Leu70Phe (c.208C>T) is associated with glioma susceptibility 2 (ClinVar).

How common is PTEN p.Leu70Phe (c.208C>T) in the general population?

PTEN p.Leu70Phe (c.208C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTEN p.Leu70Phe (c.208C>T)?

AlphaMissense predicts likely pathogenic (score 0.9945) — an in-silico prediction, not a clinical call.

PTEN p.Leu70Phe

c.208C>T · rs794727480 · VCV196250

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glioma susceptibility 2

Computational evidence

Protein change
AlphaMissense	0.9945	likely pathogenic
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -12.37	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 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Leu70Phe
Coding: c.208C>T
MANE Select: NM_000314
dbSNP: rs794727480
Type: single nucleotide variant
Location: chr10:87925556 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 70: a β-strand; the phosphatase tensin-type domain; a UniProt-annotated variant site (in mcephas); a UniProt-annotated variant site (in cws1)

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

Disease context

glioma susceptibility 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTEN p.Leu70Pro Likely pathogenic ★★★ same residue
PTEN p.Leu70Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Leu70Ile Uncertain significance ★ ⚠ same residue
PTEN c.634+2T>C Pathogenic ★★★ same condition
PTEN c.634+5G>A Pathogenic ★★★ same condition
PTEN p.Arg173Cys Pathogenic ★★★ same condition
PTEN p.Arg335Ter Pathogenic ★★★ same condition
PTEN p.Arg47Lys 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-leu70phe (accessed [today's date]).

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