I'll speculate that a freight 747 is still fundamentally structurally a plane designed to have windows (with the correspondingly reinforced fuselage) but with minor tweaks.

I'd be very surprised if that's not the case. You'd need a plane that's designed from the ground up to not have windows in any configuration.

Still, if the difference is that brutal, there would be a huge niche for planes that have no passenger version and are designed to never have windows.

Not as much as you'd expect. It's easier and cheaper to get a design with windows (and their supporting structure), and not cut out the holes for the windows in the skin. The resulting structure is going to be only marginally lighter, but also much more fatigue resistant. The savings would show up in the changed inspection intervals.