Those are exceptions rather than the rule for rare disease. Ashkenazi Jews had a bottleneck effect; SSD is a gain of function, etc. They other thing they have in common is a relatively high allele frequency in the general population.

For interference where a heterozygote would be effected (and therefore selected again) most variants would be de novo; so a homozygous mutant would require simultaneous and identical de novo mutations to occur in the same individual.