Diagnosis
This is typically caused by the monitor's adaptive sync technology conflicting with the GPU's output. The S2421HS supports AMD FreeSync.
How to Fix It
First, disable FreeSync on the monitor. Use the physical button to open the OSD. Go to Gaming > FreeSync Premium and set it to OFF. Test. If flickering stops, the issue is a driver or source signal problem. Update your GPU drivers to the latest stable version from AMD or NVIDIA. After updating, you can try re-enabling FreeSync.
If That Didn't Work
The problem may be the specific DisplayPort cable. A poor-quality cable can cause signal integrity issues that manifest as flicker. Replace it with a certified high-bandwidth DisplayPort cable.
Heads Up
If you are using an NVIDIA GPU, ensure G-SYNC Compatible mode is disabled in the NVIDIA Control Panel under 'Set up G-SYNC' if you continue to have issues with FreeSync enabled.