A fundamental feature of normal color vision is that red and green lights can be mixed to appear identical with a monochromatic yellow light. Another characteristic of normal color vision is that people often disagree on the amounts of red and green needed in the mixture to exactly match the yellow. Comparison of such color vision differences with photopigment gene differences reveals that a serine/alanine polymorphism at amino acid position 180 of X-encoded pigments can account for this type of color vision variation. This amino acid change shifts the spectrum of the pigment produced by about 6 nm, a value that would predict a larger minimum color vision difference between individuals than is actually observed. This discrepancy can be explained if, counter to the Young-Helmholtz theory as the explanation of trichromacy, many people with normal color vision have more than three spectrally different cone pigments.