You don't have to estimate any margins, the program hides them everywhere except on the outermost pages of your design, so whatever is between the dotted lines is the actual printable area. If your printer has large margins, it's best to increase the respective setting in Pepakura Designer.
That's not the way it has been working on mine. I set my margins to the smallest possible in both my printer settings and pepakura. So far i've had to shift the pieces back and estimate margins or it doesn't print. It's also not my printer because I've printed pieces out on 4 different printers. I recommend a test page.