In clinical genomics, the terms “Mendelian” or monogenic typically describe rare conditions attributed to single gene variants (otherwise known as “rare pathogenic mutations, or RPMs) that follow a well-characterized biological mechanism and predictable inheritance pattern (such as what occurs with inherited disorders like Tay Sachs or Cystic Fibrosis). Polygenic scores (PGS) estimate the genetic risk for complex conditions and traits based on the combined impact of many genetic variants (dozens to millions).