PTEN p.Pro38Ser
c.112C>T · rs587780004 · VCV127688
ClinGen expert panel — PTEN VCEP
Uncertain Significance for PTEN hamartoma tumor syndrome. Applied ACMG criteria (verbatim):
PM2_Supporting PS3_Moderate PP2 PP3
Curation rationale (ClinGen, verbatim)
NM_000314.8(PTEN):c.112C>T (p.Pro38Ser) 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). PS3_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -1.515 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PM2_P: 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 =0.957)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9998 | likely pathogenic · top 8% in PTEN |
|---|---|---|
| REVEL | 0.957 | strongly pathogenic-leaning |
| SaProt | LLR -10.28 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.27 | constrained · MANE · 69 kb · p 6.5e-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
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.Pro38Ser
- Coding
- c.112C>T
- MANE Select
- NM_000314
- dbSNP
- rs587780004
- Type
- single nucleotide variant
- Location
- chr10:87894057 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
- Residue 38
- the phosphatase tensin-type domain
Disease context
PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: hereditary neoplastic syndrome
For PTEN hamartoma tumor syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- PTEN p.Pro38His Likely pathogenic ★★★ same residue
- PTEN p.Pro38Leu Pathogenic ★★★ same residue
- PTEN p.Pro38= Likely benign ★★★ same residue
- PTEN p.Pro38Thr Likely pathogenic ★★ same residue
- PTEN p.Pro38fs Pathogenic ★ same residue
- PTEN p.Pro38Phe Likely pathogenic ★ same residue
- PTEN p.Pro38Arg Pathogenic ★ same residue
- PTEN c.1026+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-pro38ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown