Is PTEN p.Leu112Ile (c.334C>A) pathogenic?

PTEN p.Leu112Ile (c.334C>A) is classified Uncertain significance in PTEN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-01). AlphaMissense: likely pathogenic (0.8593); Absent from gnomAD v4.1; Associated with prostate cancer, hereditary, 1.

What condition is associated with PTEN p.Leu112Ile (c.334C>A)?

PTEN p.Leu112Ile (c.334C>A) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is PTEN p.Leu112Ile (c.334C>A) in the general population?

PTEN p.Leu112Ile (c.334C>A) is absent from gnomAD v4.1 (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PTEN p.Leu112Ile (c.334C>A)?

AlphaMissense predicts likely pathogenic (score 0.8593) — an in-silico prediction, not a clinical call.

PTEN p.Leu112Ile

c.334C>A · rs2132242699 · VCV2687625

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8593 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
AlphaMissense	0.8593	likely pathogenic
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -11.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.85 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 32 kb · p 4.1e-17 · regional, not allelic
Overall
CADD	29.3	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.Leu112Ile
Coding: c.334C>A
MANE Select: NM_000314
dbSNP: rs2132242699
Type: single nucleotide variant
Location: chr10:87933093 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 112: an α-helix; the phosphatase tensin-type domain; a UniProt-annotated variant site (in mcephas); a UniProt-annotated variant site (in cws1 and ldd; loss of phosphatase activity towards ins(1,3,4,5)p4); a UniProt-annotated variant site (loss of phosphatase activity towards ins(1,3,4,5)p4)

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

Disease context

prostate cancer, hereditary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

PTEN p.Leu112Val Likely pathogenic ★★★ same residue
PTEN p.Leu112fs Uncertain significance same residue
PTEN p.Leu112Arg Pathogenic ★★ same residue
PTEN p.Leu112Pro Pathogenic ★★ same residue
PTEN p.Leu112Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Leu112= Benign ★ same residue
PTEN p.Arg159Lys Pathogenic ★★★ same condition
PTEN p.Ala121Thr 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-leu112ile (accessed [today's date]).

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