A portent initially of the guys (4)
I believe the answer is:
omen
'a portent' is the definition.
(synonyms)
'initially of the guys' is the wordplay.
'initially' indicates taking the first letters.
'the guys' becomes 'men' (guy can mean a man).
The initial letter of 'of' is 'o'.
'o'+'men'='OMEN'
(Other definitions for omen that I've seen before include "Auspice" , "Straw in the wind" , "Portent, prophetic sign" , "Sign of a future event, good or bad" , "Warning token" .)