PTEN p.Ala39Ser
c.115G>T · VCV4908603
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.5989 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5989 | likely pathogenic |
|---|---|---|
| REVEL | 0.725 | pathogenic-leaning |
| SaProt | LLR -9.33 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss, 49 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 9.8 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.27 | constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic |
| Overall | ||
| CADD | 25.9 | PHRED · no single calibrated threshold — expert panels disagree |
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.Ala39Ser
- Coding
- c.115G>T
- MANE Select
- NM_000314
- Type
- single nucleotide variant
- Location
- chr10:87894060 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
- Residue 39
- a β-strand; the phosphatase tensin-type domain
Similar variants
- PTEN p.Ala39Thr Likely pathogenic ★★★ same residue
- PTEN p.Ala39Val Likely pathogenic ★★★ same residue
- PTEN p.Ala39= Benign/Likely benign ★★ same residue
- PTEN p.Ala39Pro Likely pathogenic ★ same residue
- PTEN p.Ala39Glu Uncertain significance ★ ⚠ same residue
- PTEN c.1026+1G>A Pathogenic ★★★ same type
- PTEN c.1027-1852A>G Likely pathogenic ★★★ same type
- PTEN c.1027-1G>A Pathogenic ★★★ same type
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-ala39ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown