100%- it sure as hell ain't some magic spell of March or some other hocus pocus BS that sports announcers want you to believe. I think some of the 5 seeds tend to be public teams that they were highly enamored with during the season as they were Final Four hopefuls or in the Top 10 at some point and the public continues to hold onto that during the NCAAT not realizing they are overrating them. In addition to that, the #5 is from a power conference and looks mightier than the #12 from a "measly" mid major by comparison that no would ever imagine going to the Sweet 16 in the middle of the regular season, well for the most part.
33% of the time according to navery12's post, IMO, is a high amount. I do wonder about winning % of 6-11, 7-10, 4-13, and 3-14 matchups in comparison to the 5-12 matchup. I will Google it later