Your question starts with a misconception. Resistance to smallpox is not inherited and European colonialists had no innate immunity to the disease.^* Smallpox continued to cause epidemics and deaths in Europe (and among Europeans in the Americas). Europeans that traveled to the Americas from places where smallpox was endemic (always present) were largely immune to the disease for three reasons:
Survived a previous smallpox infection
Been exposed inadvertently to a weakened form of the virus though the environment
Been exposed to the virus as an infant while still protected by maternal antibodies
The populations of the Americas did not have a these factors, so when smallpox was first introduced it affected all levels of the population equally, rather than largely killing off young people and leaving an immunized adult population.
Colonial populations, particularly those born in the Americas, often lacked these factors for acquiring immunity, which meant that smallpox outbreaks could affect them quite severely. Fenn's Pox Americana notes that one of the reasons the smallpox epidemic between 1775-1782 in what was becoming the United States was so notable was because there was a significant population of European-descended/Colonial-born people who did not have the chance to acquire immunity like European-born colonists.
^(*Someone might say something here about the CCR5-delta32 mutation, but the connection between that and smallpox immunity is still hypothetical. There have been, for obvious reasons, no clinical studies showing whether the mutation protects against smallpox and, if it does, to what extent.)