Final answer:
Rare/de novo gene variants are often more associated with negative consequences because they have not undergone extensive natural selection and their harmful effects may not have been 'filtered' out. They can lead to abnormalities and disease susceptibilities, particularly in isolated or endogamous populations. Common variants have been more thoroughly studied and might not be as severely disadvantageous.
Step-by-step explanation:
We might expect rare/de novo gene variants to be more associated with negative consequences than common variants because they have not been subjected to extensive natural selection which tends to weed out variants that are deleterious to health. These rare variants can lead to genotypic and phenotypic abnormalities and susceptibilities to disease. Often, such mutations arise spontaneously and have not been through the 'filter' of generations of survivors which generally removes harmful variants. Additionally, if these variants are recessive, they are unlikely to be selected against until they are in a homozygous state, which is rare unless there is inbreeding, as seen in certain isolated or endogamous populations.
Common variants, on the other hand, have persisted through many generations, indicating that they might not be severely disadvantageous or may even be neutral or beneficial. The prevalence of common variants also means that their effects, whether harmful or not, are possibly well understood as they have been subjected to more thorough scientific study due to their higher occurrence in the population.
Finally, the identification of disease-causing genetic variations often requires comparing the genomes of large numbers of individuals with and without a disease to discern which variations may have significant effects on disease risk. This approach identifies not only single nucleotide polymorphisms (SNPs) but also structural variations such as duplications, deletions, insertions, inversions, and translocations, that can have even greater impacts on an individual's phenotype.