Umpires Ian Gould and Rod Tucker were forced to change the ball, and apply a five-run penalty, after they deemed the condition of the ball had been changed as the Proteas were pushing for victory late into the day.
South Africa captain Graeme Smith was called over by the umpires at the end of the 30th over - two overs after tea - and informed of the decision to enforce the penalty.
No South Africa player has yet been charged, but TV replays appeared to show a player - believed to be all-rounder Faf du Plessis - rubbing the ball against the zipper on his whites.
However, the Proteas swiftly denied any suggestions of cheating at stumps, which arrived with Pakistan on 132 for four in their second innings - still trailing by 286.
"We are not a team that scratches the ball," wicketkeeper-batsman De Villiers was quoted by Cricinfo as saying at the post-match press conference.
"We play in a fair manner. We want to swing the ball as much as we can. We try and get it to reverse, putting more sweat on one side and things like that. But we don't cheat. It's as simple as that."
De Villiers particularly spoke up for team-mate Du Plessis, who was also brought into the on-field meeting between Smith and the match officials.
"I know Faf very well," the 29-year-old added. "He is the last man on the field who will try anything like that.
"It is part of his responsibility to shine the ball, in order to get it to swing, and look after it. It is not an easy job and I thought he did a very good job of it."
Further sanctions could be applied on top of the five-run penalty, with an ICC spokesman confirming to Press Association Sport that any player reported for ball tampering by the umpires would be subject to a hearing in front of the match
referee as a matter of process.
Under the ICC regulations the umpires are obligated to report the incident to match referee David Boon, who is expected to call a hearing.
Playing regulation 42.1 (e) reads: "Together with the other umpire report the incident to the ICC match referee who shall take action as is appropriate against the player(s) responsible for the conduct under the ICC code of conduct.
"If the ICC match referee is unable to identify the player(s) responsible for such conduct, the captain shall take responsibility and will be subject to such action as is appropriate under the ICC code of conduct."
Altering the condition of the ball is a level two offence under the ICC's code of conduct, which carries a penalty of 50 per cent to 100 per cent of their match fee and/or suspension from one Test or two one-day internationals for a first offence.