PTEN p.Ile33=
c.99T>C · rs786201650 · VCV184734
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.26 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.1 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 16.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,178,646 alleles
Overall
6.85e-05%
1/1,459,872 alleles · very rare
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PTEN
- Protein
- p.Ile33=
- Coding
- c.99T>C
- MANE Select
- NM_000314
- dbSNP
- rs786201650
- Type
- single nucleotide variant
- Location
- chr10:87894044 (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)
Similar variants
- PTEN p.Ile33Thr Uncertain significance ★★★ ⚠ same residue
- PTEN p.Ile33Met Uncertain significance ★★ ⚠ same residue
- PTEN p.Ile33del Likely pathogenic ★★★ same residue
- PTEN p.Ile33fs Pathogenic ★★ same residue
- PTEN p.Ile33Asn Uncertain significance ★★ ⚠ same residue
- PTEN c.1026+1G>A Pathogenic ★★★ same condition
- PTEN c.1027-1852A>G Likely pathogenic ★★★ same condition
- PTEN c.1027-1G>A 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-ile33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown