Yes, this can happen and is known as underdominance and is a specific type of epistasis (which is a more complex, but more realistic view of the interaction between alleles than the simple dominant/recessive model that is taught in intro biology). The thing is, if the disease is severe, then selection will be very strong against heterozygotes. If the population is otherwise freely mixing, whichever allele is less common would pretty quickly get removed, so such examples will never be common. If the alleles segregate among sub-populations that don't mix freely, then this kind of thing is likely a contributing factor to speciation (see the Dobzhansky–Muller model, though if you want to look at the most current research on this idea, "cryptic variation" is the umbrella term that you should use)
WildZontar t1_ja9dsab wrote
Reply to Is there a genetic disease where the heterozygote has more severe disease symptoms than the homozygote? by Altranite-
Yes, this can happen and is known as underdominance and is a specific type of epistasis (which is a more complex, but more realistic view of the interaction between alleles than the simple dominant/recessive model that is taught in intro biology). The thing is, if the disease is severe, then selection will be very strong against heterozygotes. If the population is otherwise freely mixing, whichever allele is less common would pretty quickly get removed, so such examples will never be common. If the alleles segregate among sub-populations that don't mix freely, then this kind of thing is likely a contributing factor to speciation (see the Dobzhansky–Muller model, though if you want to look at the most current research on this idea, "cryptic variation" is the umbrella term that you should use)