PTEN p.Pro38His
c.113C>A · rs1064796886 · VCV1012092
ClinGen expert panel — PTEN VCEP
Likely Pathogenic for PTEN hamartoma tumor syndrome. Applied ACMG criteria (verbatim):
PM6 PM2_Supporting PS3_Moderate PS2
Curation rationale (ClinGen, verbatim)
PTEN c.113C>A (p.Pro38His) meets criteria to be classified as Pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.2.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor SCV005079984.1) PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (internal laboratory contributor SCV005079984.1) PS3_moderate: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = [-4.783403086] (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PM2_supporting: Absent in large sequenced populations in the gnomAD v4 cohort. (PMID 27535533).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9999 | likely pathogenic ✓ concordant with ClinVar · top 8% in PTEN |
|---|---|---|
| REVEL | 0.95 | strongly pathogenic-leaning |
| SaProt | LLR -13.60 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.47 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.27 | constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
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.Pro38His
- Coding
- c.113C>A
- MANE Select
- NM_000314
- dbSNP
- rs1064796886
- Type
- single nucleotide variant
- Location
- chr10:87894058 (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 & treatmentsFor PTEN hamartoma tumor syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- PTEN p.Pro38Leu Pathogenic ★★★ same residue
- PTEN p.Pro38Ser Uncertain significance ★★★ ⚠ same residue
- PTEN p.Pro38= Likely benign ★★★ same residue
- PTEN p.Pro38fs Pathogenic ★ same residue
- PTEN p.Pro38Phe Likely pathogenic ★ same residue
- PTEN p.Pro38Thr 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-pro38his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown