On PopGen the issue is not mistrust on the model if the assumptions hold. I would find it completely revolutionary that results would be different from expected theoretical results on a completely controlled experiment. Actually I think Mendel did what you want for traits (which, by sheer luck, mapped in a clear way to genes).
The problem is that, in real life there are massive deviations from models that are constructed and a) many of those deviations are both unknown (in many cases you don't know say, mating behavior) and b) their effects are not properly quantified. But, if you know all about your species and history (mating, behavior, population structure) you can construct a model which should provide realistic results. The underlying genetic mechanisms are reasonably well known.

Another, different problem, is when you know very little of the core properties of systems in order to model them. For instance for many drugs pharmacological properties' are not known. So any model that is created has a much bigger amount of speculation (has the core behavior is not known).

Of all forms of caution, caution in love is perhaps the most fatal to true happiness - Bertrand Russell