A specific variant in SLC24A5, called rs1426654, is one of the single largest genetic contributors to the difference in skin pigmentation between Europeans and Africans.

This variant is found at high frequencies in modern European and South Asian populations but is rare in African populations.

HERC2/OCA2: this genomic region contains regulatory elements that control the expression of OCA2, a gene involved in melanin production in the eye and skin.

A specific variant in the HERC2 region reduces OCA2 expression and is strongly associated with blue eye color in Europeans.

The analysis of these specific variants — along with many others — in Cheddar Man’s genome is what produced the pigmentation prediction.