Moolman-Pasio, who races for the Swiss-based Bigla Pro team, overcame mechanicals and a high-speed crash to claim a hard-fought victory in a tough international field.
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Dutch cyclists Sabrina Stultiens and Floortje Mackaij claimed second and third place respectively for Team Liv Plantur.
Arriving at the start with a malfunctioning front derailleur, Moolman-Pasio was forced to fix her chain ring on the big gear, putting her at a disadvantage from the outset.
The women’s peloton exploded on the first major climb of the day with a flurry of attacks into Joe Slovo Drive.
Then, on the Nelson Mandela Bridge, Moolman-Pasio hit a pothole and crashed heavily.
Suspecting she might have a broken collarbone, the determined Commonwealth Games medallist got back in the saddle and chased back.
“I was quite shocked as it was a high speed crash. I checked if everything was okay and had to settle my nerves but my team was absolutely fantastic today,” said Moolman-Pasio.
“They chased with absolute heart to bring back the breakaway and put the pressure on at the climbs.”
When teammate Sharon Laws went on the attack and rode away from the two Dutch leaders in the final 10km stretch, Moolman-Pasio saw her opportunity.
“She set me up beautifully. I tried to encourage her to come with me but I think the hard work had taken its toll.”
The South African put her head down and rode away for an uncontested win to the delight of the local fans.