Clark limped off during Northampton's semi-final win against Saracens and he has failed to recover in time for the Saints' Twickenham showdown with Leicester.
The 23-year-old will be assessed by the England medics on Sunday and a decision made as to whether he will once again have to drop out of national duty.
Clark was ruled out of England's 2012 summer tour of South Africa and the autumn internationals that followed after receiving a record 32-week ban for breaking the arm of Leicester hooker Rob Hawkins.
England head coach Stuart Lancaster stood by Clark and he was recalled for the Six Nations, only to suffer a shoulder injury in January that sidelined him for the whole tournament.
Clark was selected again for England's three-match tour, which starts against a combined South American XV in Montevideo a week tomorrow before two Tests against Argentina.
Phil Dowson will start at blindside flanker for Northampton on Saturday afternoon as the Saints go in search of their first Premiership title.