__instancecheck__ is not only slower, it can also cause crashes:

import abc
class MyABC:
    __metaclass__ = abc.ABCMeta
    __slots__ = ["a"]

class Unrelated:
    pass
MyABC.register(Unrelated)

u=Unrelated()
assert isinstance(u, MyABC)

MyABC.a.__set__(u, 3) # Boom


The patch I proposed above correctly raises the error:
TypeError: descriptor 'a' for 'MyABC' objects doesn't apply to
'Unrelated' object