Freiburg appeared to have gotten off the hook before half-time as defender Marc-Oliver Kempf looked to have handled the ball only for the incident not to be picked up.
After a delay of six minutes, Mainz were 1-0 up.
Defeat meant Freiburg dropped behind Mainz into the relegation zone due to an inferior goal-difference, with four games of the season remaining.
76ers roll on without Embiid
Embiid, who did not feature in Game 1 , will not be featuring in Game 2 on Monday either despite clearing the concussion protocol. Embiid has been ruled out for Monday's Game 2 as he continues to recover from surgery to fix an orbital bone fracture.
The players had already gone off for the interval when the German official Guido Winkmann consulted the video assistant referee (VAR) about a Freiburg handball in the last moments of the first-half.
Freiburg's players had to be summoned from the dressing room and back onto the pitch to allow the home side to take their penalty.
"It leaves a bitter taste", Freiburg sporting director Jochen Saier said.
VAR was introduced to eradicate refereeing mistakes and make the game smoother, so far it's only brought chaos though..
Pep Guardiola makes huge claim over Man Utd and Chelsea decision
When I heard pundits and fans in November they said it's all done, it's impossible for City to drop points. If we lose we're going to do it in a similar way to the way we played against United and Liverpool.
A Bundesliga match descended into chaos as the referee awarded a penalty during half-time after checking the VAR.
Indeed, the goal proved to be a major turning point and Mainz put the seal on a crucial victory in the 79th minute when De Blasis capitalised on a awful goalkeeping error to slot home.
Supporters also forced the game to be paused by throwing rolls of toilet paper on to the pitch as a protest against the Bundesliga's introduction of matches on Monday nights.
De Blasis, who'd had to wait for Alexander Schwolow to re-take his place in goal, held his nerve to score inside the left corner as the Freiburg 'keeper dived the other way.
The irrelevancy of Paul Ryan
Last August he told a CNN forum that the president "messed up" his original response to the racist violence in Charlottesville. Casey notes that numerous Republicans choosing to leave Washington right now are more moderate on the political spectrum.