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The 21 year-old arrived at Stade Toulousain last summer from Grenoble, and has caught the attention of the French selectors with his pace and ability to score tries, bagging six for Toulouse so far this season.
Clerc said: "I visited the Centre National de Rugby (France base camp) last February with the under-21s and this couldn't have been further from my mind. It is a huge honour to be part of the team and I am quickly getting used to the moves and the routine.
"Our objective is to win all three matches to increase our confidence looking ahead to the World Cup - that gives a totally different dimension to these short term goals."
Cédric Heymans, also of Toulouse, is another surprise selection and comes in over David Bory who is left out of the 22.
Although France have had to shuffle their backline due to injuries to Clement Poitrenaud and Tony Marsh, coach Bernard Laporte believes this could be beneficial to France in the long term.
"I don't fear for our lack of experience in our backline," said Laporte.
"A year ago, we had to incorporate a lot of young forwards due to injuries, but we did it with some success. It also enables us to increase our reservoir of players.
"South Africa only needed one match to position themselves as one of the big favourites for the next World Cup, they are a team of great note. We owe it to ourselves to beat them, so that we too position ourselves as candidates for that title.
"The South Africans have revolutionised their game. They have gone against their traditional style. They now play with the ball in hand a lot and they have gone for attack in a big way.
"It is a huge joy to return to the Stade Vélodrome in Marseille. It is hugely exciting to rediscover this crowd who get behind their team to such an extent. It is a bit like meeting the most beautiful girl in the village!"
