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Despite injury concerns over Yoann Maestri, who Vahaamahina replaced last time out, it is Christophe Samson who drops to the bench, with the Toulouse lock keeping his spot.
In the back row Claassen will also make his first start, having come off the bench in the last two games against England and Ireland.
The final change sees Mathieu Bastareaud come back into the centres in place of Florian Fritz. The Toulouse centre has been struggling with injury this week so uncapped 18-year-old Gaël Fickou has been named as back-up on the bench.
Saint-André said: “We decided to make a couple of changes up front to cope with the particularities of this Scottish team, as well as the weather conditions because it’s set to rain a lot at the Stade de France on Saturday.
“We wanted a little more power up front with Vahaamahina in the second row, and Claassens at six.
“In the three-quarters Fritz has been struggling so it makes sense that Mathieu starts.”
15 Yoann Huget (Toulouse)
14 Vincent Clerc (Toulouse)
13 Mathieu Bastareaud (Toulon)
12 Wesley Fofana (Clermont)
11 Maxime Médard (Toulouse)
10 Frédéric Michalak (Toulon)
9 Morgan Parra (Clermont)
1 Thomas Domingo (Clermont)
2 Benjamin Kayser (Clermont)
3 Nicolas Mas (Perpignan)
4 Sébastien Vahaamahina (Perpignan)
5 Yoann Maestri (Toulouse)
6 Antonie Claassen (Castres)
7 Thierry Dusautoir (Toulouse) captain
8 Louis Picamoles (Toulouse)
16 Guilhem Guirado (Perpignan)
17 Vincent Debaty (Clermont)
18 Luc Ducalcon (Racing Métro)
19 Christophe Samson (Castres)
20 Yannick Nyanga (Toulouse)
21 Maxime Machenaud (Racing Métro)
22 François Trinh-Duc (Montpellier)
23 Florian Fritz/Gaël Fickou (both Toulouse)