PTEN p.Ile33del
c.94ATT[1] · rs1554893765 · VCV449088
ClinGen expert panel — PTEN VCEP
Likely Pathogenic for PTEN hamartoma tumor syndrome. Applied ACMG criteria (verbatim):
PM2_Supporting PM6_Strong PS3_Moderate PP1
Curation rationale (ClinGen, verbatim)
PTEN c.97_99delATT (c.94ATT[1]) (p.Ile33del) meets criteria to be classified as likely pathogenic 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). PS3_Moderate: Phosphatase activity ≤ -1.11 per Mighell et al. 2018, PMID: 29706350. PM2_Supporting: Absent in large sequenced populations (PMID 27535533). PM6_Strong: An individual with a highly specific phenotype (Internal laboratory contributor SCV000616838.1). PP1: Co-segregation with disease in multiple affected family members, with 5 or 6 meioses observed. (PMID 10234502 , internal laboratory contributor SCV002559099.1)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -0.15, phastCons 1 |
Population frequency
No gnomAD frequency available for this variant. 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.Ile33del
- Coding
- c.94ATT[1]
- MANE Select
- NM_000314
- dbSNP
- rs1554893765
- Type
- Microsatellite
- Location
- chr10:87894039 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
- Residue 33
- a β-strand; the phosphatase tensin-type domain; a UniProt-annotated variant site (in cws1)
Disease context
PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Cowden syndrome 1hereditary neoplastic syndrome
For PTEN hamartoma tumor syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- PTEN p.Ile33Thr Uncertain significance ★★★ ⚠ same residue
- PTEN p.Ile33fs Pathogenic ★★ same residue
- PTEN p.Ile33Asn Uncertain significance ★★ ⚠ same residue
- PTEN p.Ile33Met Uncertain significance ★★ ⚠ same residue
- PTEN p.Ile33= Likely benign ★ same residue
- PTEN p.Asp52del Likely pathogenic ★★★ same condition
- PTEN p.Tyr178del Likely pathogenic ★★★ same condition
- PTEN p.Met199del Uncertain significance ★★★ 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-ile33del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown