PTEN p.Leu182Ser
c.545T>C · rs794729664 · VCV187827
ClinGen expert panel — PTEN VCEP
Uncertain Significance for PTEN hamartoma tumor syndrome. Applied ACMG criteria (verbatim):
PM2_Supporting PP2 PP3
Curation rationale (ClinGen, verbatim)
PTEN c.545T>C (p.Leu182Ser) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). Of note, this variant may be disease-causing when present in the homozygous state (PMID: 26443266), but this expert panel curation is based on presence in the heterozygous state. PM2: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: REVEL score > 0.7 (score of this variant =0.972)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.947 | likely pathogenic |
|---|---|---|
| REVEL | 0.972 | strongly pathogenic-leaning |
| SaProt | LLR -11.05 | 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 7.9 | GERP 2.9, phastCons 1 |
| Regional constraint | o/e 0.51 | unconstrained · MANE · 32 kb · p 4.1e-17 · regional, not allelic |
| Overall | ||
| CADD | 29.7 | 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
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.Leu182Ser
- Coding
- c.545T>C
- MANE Select
- NM_000314
- dbSNP
- rs794729664
- Type
- single nucleotide variant
- Location
- chr10:87952170 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
- Residue 182
- an α-helix; the phosphatase tensin-type domain; a UniProt-annotated variant site (in mcephas)
Disease context
PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Cowden syndrome 1macrocephaly-autism syndrome
For PTEN hamartoma tumor syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- PTEN p.Leu182Ter Pathogenic ★★ same residue
- PTEN p.Leu182= Benign/Likely benign ★★ same residue
- PTEN p.Leu182_Lys183insTer Pathogenic ★★ same residue
- PTEN p.Leu182_Lys183delinsTer Pathogenic ★ same residue
- PTEN p.Leu182fs Pathogenic ★ same residue
- PTEN p.Leu182Phe Uncertain significance ★ same residue
- PTEN c.1026+1G>A Pathogenic ★★★ same condition
- PTEN c.1027-1852A>G 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-leu182ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown