Wise guys, most are genuinely ignorant, first of all (4)
I believe the answer is:
magi
'wise guys' is the definition.
(I've seen this in another clue)
'most are genuinely ignorant first of all' is the wordplay.
'first of all' indicates taking the first letters.
The initial letters of 'most are genuinely ignorant' is 'MAGI'.
(Other definitions for magi that I've seen before include "Three Wise Men of the Bible" , "Nativity story wise men" , "The three Wise Men of the gospels" , "Priests" , "Star witnesses" .)