How many rare variants does each of us carry? This is analogous to the classic question of genetic load and the average number of recessive lethals per individual. Given the likely average frequency of rare variants (though the frequency distribution is probably very skewed), and the many thousands of genes in which such variants could occur, it seems possible that the average number of rare variants per person could easily be ten or more. As it is almost only the rare variants that are associated with high enough penetrances to influence individual prophylactic decisions, it is this type of low frequency variation that may be much more likely to become the basis for some sort of personalized medicine, than that usually discussed in relation to common polymorphic variation.
