depends on how handy you are. If you are literally building from scratch then you are making your own frame so no. If you are buying a frame setup for an existing engine, yeah it might. Harley engines are not symmetrical like brits, Japanese, etc... Even some of the Japanese frames from the 70's and 80's are not truly symmetrical, the cb750F for instance has more clearance on one side of the frame than the other specifically to address chain line (the swingarm pivot is not symmetrical either to compensate).Would that matter if you're building the bike from scratch?