I am working on a variable font with 6 axes (weight, width, round, etc.). There are two masters for each axis, for example, the weight axis has 2 masters (light & black). Do I have to create 22222*2=64 masters?
Technically you can leave empty corners, but in most cases they won’t look good. Also, don’t forget to have fun if you have any intermediate layers 
From experience I can say that yes, you do need all of them.
Can you share all of the axes?
Maybe you can get away with fewer. E.g., for a Grade axis you would not need to duplicate your masters.
Width, Round Corner, Right Stem Weight, Left Stem Weight, Horizontal Bar Weight, X-Height.
I actually solved it with fewer master. Here is what I did.
The combinations in the first pic is what I would have to do, which would be overwhelming. Instead I chose to create masters as shown in the second image. In the pic, the orange coloured rows (masters) become redundant, So I created only one.
Pic 1:
Pic 2:
PS: I will write in detail about this.
Do you mind elaborating please? In a variable font? Or filter on instances?
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