KL Rahul and Kuldeep Yadav have been ruled out of the South African series; Pant will take over.
Replacements for the two injured cricketers have yet to be identified by the selection committee.
India's T20I squad: Rishabh Pant (Captain)(wk), Hardik Pandya (vice-captain), Ruturaj Gaikwad, Ishan Kishan, Deepak Hooda, Shreyas Iyer, Dinesh Karthik (wk), Venkatesh Iyer, Yuzvendra Chahal, Axar Patel, Ravi Bishnoi, Bhuvneshwar Kumar, Harshal Patel, Avesh Khan, Arshdeep Singh, Umran Malik
Rahul has been ruled out of the series due to a right groin injury, while Kuldeep Yadav sustained an injury while batting in the nets a few days before the start.
"Both players will now report to the NCA, where the medical experts will examine them further and determine the best course of treatment," the BCCI said in a statement.
On Tuesday, Rahul was absent from India's practice session (June 8). "On Wednesday morning, he complained of pain and was examined. As a precaution, and with the England series in mind, the team management determined that he would be pulled from the South Africa series "According to a source familiar with the situation,
Rahul's ailment is said to be a recurring one, which is why he was unable to play in the Sri Lanka series. He had scans during the recently finished Indian Premier League (IPL), but nothing significant was discovered, and he was able to play comfortably.
Rahul's participation on the England trip, for which he was selected vice-captain under Rohit Sharma, is yet unknown.
When Rahul's scheduled pre-match press conference on Wednesday evening was postponed, it was the first hint of his unavailability.
Due to Rahul's absence, Pant, the captain, has a chance to shine. The 24-year-old Delhi Capitals captain has had a stratospheric rise since his readmission to India's T20I set-up in the home series against England a little over a year ago.