Large-scale sequencing of the human population has shaped the current understanding of naturally occurring genetic sequence variation. Each human contains approximately 3 million to 5 million , including approximately 30 000 variants in protein-coding genes, when compared with the reference genome. In the case of , only 1 or 2 of these variants may be relevant to a molecular diagnosis. Many lines of evidence are required to determine whether a particular variant is likely to cause or contribute to the development of disease, but one powerful discriminator is allele frequency. Allele frequency is defined as the proportion of (2 per individual) that carry a particular variant at a specific location in the genome.