I always start with the default setting for proofgrade leather and adjust from there depending on the thickness of the leather. (Hopefully you have a set of calipers so you can get accurate measurement for your leather!) The PG leather thicknesses are; thin approx 1/48", medium approx 3/64" & thick approx 3/32". So if your leather is close to one of those measurement, just use the pull-down menu to enter the PG leather setting and do a little testing from there.
I would highly suggest using some hold-down pins for the leather and if you are cutting something, look very carefully to make sure it cut all the way through before moving the leather off the GF tray. That way you can make another cutting pass without any aliment issues.
These were two leather conversations I had bookmarked that may have some good info for you. Good luck!