Double blow for Boks
The prop suffered an ankle injury against Ireland in the dramatic come-from-behind 32-26 victory in the second Test between the sides last Saturday in Johannesburg.
Nyakane was sent for x-rays on Monday, which showed no fracture except for some swelling.
However, further assessment on Tuesday morning revealed that Nyakane will not be ready to be considered for Saturday's decisive third Test.
A substitution to serve as extra cover for both the loosehead and tighthead positions, will be named in due course.
Nyakane joins No.8 Duane Vermeulen (elbow) and De Jager (calf) on the injury list.
All three players have left the Springbok camp.
The Bok management has confirmed that three players, Siyabonga Ntubeni (Stormers), Nic Groom (Stormers) and Garth April (C Sharks), will return to their franchises on Tuesday.
The Springboks continued their preparations on Tuesday with an extended training session at the Nelson Mandela Bay Stadium.
South Africa and Ireland are tied at one-all in the series - after the Irish won the first Test (26-20) at Newlands on June 11 and the Boks bounced back to win (32-26) at Ellis Park last Saturday - SA twice coming back from being 6 points down, 3-19 at half-time and 10-26 going into the final quarter.
The teams are also tied on 52 points each for the three-match series.