The 32-year-old hooker picked up the injury in training last week leaving head coach Joe Schmidt with just two available hookers.
While South Africa head coach Heyneke Meyer has named an unchanged starting XV from the one that defeated the All Blacks 27-25 in October, Schmidt has 17 internationals, including Best, unavailable for the Aviva Stadium encounter.
“His calf strain that has been slower to heal than expected,” the IRFU confirmed on their website. “He is partaking in modified training but a decision has been made not to risk him this weekend and his progress will continue to be monitored.”
Leinster duo Sean Cronin and Pretoria-born Richardt Strauss are left to compete for the starting berth against the Springboks ahead of their team announcement on Thursday as Best undergoes modified training.
Strauss made his debut against the country of his birth in Dublin two years ago and could again go up against his cousin Adriaan Strauss, who starts on the bench.
Meyer has had the rare luxury of naming an unchanged starting XV from the one that enjoyed a famous win over New Zealand, with his only change coming on the bench as Coenie Oosthuizen comes in for injured lock Marcel van der Merwe.
“It’s only the fifth time in what will be the 34th Test since I was appointed as Springbok coach that we’ve been able to select an unchanged starting line-up,” Meyer said.
“In this day and age, not making changes to teams is pretty much unheard of, but this is a great position we’re in.
“However, we need to make it count against a very tough Irish side on Saturday.
“Although we won our last Test, the challenge this week is to make another step up. It’s imperative that we improve in all facets of our play.”
South Africa: Willie le Roux; Cornal Hendricks, Jan Serfontein, Jean de Villiers (captain), Bryan Habana, Handré Pollard, Francois Hougaard; Tendai Mtawarira, Bismarck du Plessis, Jannie du Plessis, Eben Etzebeth, Victor Matfield, Marcell Coetzee, Teboho Mohoje, Duane Vermeulen
Replacements: Adriaan Strauss, Trevor Nyakane, Coenie Oosthuizen, Bakkies Botha, Schalk Burger, Cobus Reinach, Pat Lambie, JP Pietersen
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