Sheer trouble with unknown unorthodoxy (6)
I believe the answer is:
heresy
'unorthodoxy' is the definition.
(synonyms)
'sheer trouble with unknown' is the wordplay.
'trouble with' indicates an anagram.
'unknown' becomes 'y' (algebra).
'sheer' anagrammed with 'y' can make 'HERESY'.
(Other definitions for heresy that I've seen before include "Iconoclasm" , "Opinion opposed to orthodox belief" , "Opinion opposed to orthodox religious teachings" , "Unorthodox doctrine" , "Belief that's anathema to the orthodox" .)