Rare fragile sites are found in less than 5% of the population, and are often composed of two- or three-nucleotide repeats. They are often susceptible to spontaneous breakage during replication, frequently affecting neighboring genes. Clinically, the most important rare fragile site is FRAXA, which is associated with the fragile X syndrome, the most common cause of hereditary intellectual disability. For detailed information regarding each characterized fragile site, please visit HumCFS: a database of fragile sites in human chromosomes, published in BMC Genomics.