Example:
What is/are important are not your mistakes, but how you respond to them.
Which option makes more sense grammatically?
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What is/are important are not your mistakes, but how you respond to them.
Which option makes more sense grammatically?
Neither of them make sense, grammatically, because mistakes is plural and how you respond is singular.
If we are forced to make a choice between the two, the best option would be to use is, because it's less of a stretch to consider mistakes as a collection (that is a singular set of mistakes), than it is to try to justify writing What are important is (or are) how you respond . . . .
I would personally not be comfortable writing mistakes is in this context, however, at least not in and I'm a pretty liberal grammarian (sometimes even a grammamatician). In conversational speech, it's the kind of thing many of us do without many others noticing or caring much.
The better option would be to re-write around the problem, for example:
It is not your mistakes that are important, it is how you respond to them.