The 20-year-old captained South Africa to the IRB Junior World Championship last year and, along with another inclusion from that side, loose-forward Pieter-Steph du Toit of the Sharks, is viewed as one of the bright young things of South African rugby.
"It's good to see Jan and Pieter-Steph make the step up from the junior levels. I've always rated them and they've shone this year for the Bulls and Sharks," Springboks coach Heyneke Meyer told a press conference on Saturday night.
Among the other uncapped players, four have not been part of the national set-up before. They are the Cheetahs quartet of front-rowers Lourens Adriaanse and Trevor Nyakane, flanker Lappies Labuschagne and winger Willie le Roux.
The other three remaining uncapped players are Stormers flanker Siya Kolisi and the Bulls pair of loose-forward Arno Botha and scrumhalf Jano Vermaak.
Meyer has also selected overseas-based scrumhalf Ruan Pienaar from Ulster and Bath flanker Francois Louw, but maintains he prefers to pick players plying their trade in South Africa.
"I have always said I want to pick the guys in South Africa first. Ruan and Francois are the only overseas we have considered for the moment," Meyer said.
"If there are injuries then we might have to look at more guys overseas and there are some quality guys there.
"I am very happy with this squad, there are a lot of youngsters coming through and you have to back them and the other guys playing in South Africa."
The Springboks open their four nations tournament against Italy in Durban next Saturday, before a meeting with Scotland in Nelspruit on June 15.
There will be a final round of matches in Pretoria on June 22, with the fixtures to be determined by results on the opening two weekends.
Forwards (19): Tendai Mtawarira, Lourens Adriaanse, Trevor Nyakane, Jannie du Plessis, Coenie Oosthuizen, Adriaan Strauss, Bismarck du Plessis, Chiliboy Ralepelle, Eben Etzebeth, Flip van der Merwe, Juandré Kruger, Pieter-Steph du Toit, Siya Kolisi, Francois Louw, Marcell Coetzee, Willem Alberts, Arno Botha, Lappies Labuschagne, Pierre Spies.
Backs (15): Jano Vermaak, Ruan Pienaar, Francois Hougaard, Pat Lambie, Morné Steyn, Jean de Villiers, Juan de Jongh, Jan Serfontein, JJ Engelbrecht, Bryan Habana, Lwazi Mvovo, Bjorn Basson, Gio Aplon, Zane Kirchner, Willie le Roux.