PTEN p.Arg15Lys
c.44G>A · rs398123324 · VCV404147
ClinGen expert panel — PTEN VCEP
Likely Pathogenic for PTEN hamartoma tumor syndrome. Applied ACMG criteria (verbatim):
PM2_Supporting PM6_Strong PS3_Moderate PP2
Curation rationale (ClinGen, verbatim)
NM_000314.8(PTEN):c.44G>A (p.Arg15Lys) 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 3.1.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM2_P: Absent in large sequenced populations (PMID 27535533). PM6_S: One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype. (internal laboratory contributor: SCV000573362.4) 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. PS3_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -1.65 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9964 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.7 | pathogenic-leaning |
| SaProt | LLR -11.97 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.27 | constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic |
| Overall | ||
| CADD | 27.6 | 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.Arg15Lys
- Coding
- c.44G>A
- MANE Select
- NM_000314
- dbSNP
- rs398123324
- Type
- single nucleotide variant
- Location
- chr10:87864513 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
- Residue 15
- the phosphatase tensin-type domain; a UniProt-annotated variant site (in cws1; also found in glioma)
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.Arg15Thr Likely pathogenic ★★★ same residue
- PTEN p.Arg15Ser Pathogenic/Likely pathogenic ★★ same residue
- PTEN p.Arg15Ter Pathogenic ★★ same residue
- PTEN p.Arg15del Uncertain significance ★★★ same residue
- PTEN p.Arg15Ile Likely pathogenic ★★ same residue
- PTEN p.Arg15Gly Likely pathogenic ★ same residue
- PTEN p.Arg15= Benign ★ 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-arg15lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown