Table 3 Set of nsSNPs indicated by structure-based methods to be detrimental.

SNP IDs	Mutation	I-Mutant		CUPSAT (Thermal)		CUPSAT (Denature)		MUpro (Increase ↑ or Decrease ↓)				Align-GVGD
SNP IDs	Mutation	A	B	A	B	A	B	SVM	NN	SV0M	NN	Align-GVGD
rs5743316	N284I	↓stability	↓stability	Stabilizing	Stabilizing	Destabilizing	Destabilizing	↑	↑	↓	↓	Most likely
rs752889035	C37R	↓stability	↓stability	Destabilizing	Destabilizing	Stabilizing	Stabilizing	↑	↓	↓	↓	Most likely
rs760275329	Q538P	↓stability	↓stability	Stabilizing	Destabilizing	Destabilizing	Destabilizing	↓	↓	↓	↓	Most likely
rs768091235	L360P	↓stability	↓stability	Destabilizing	Destabilizing	Stabilizing	Stabilizing	↓	↓	↓	↓	Most likely

*Note: I-Mutant: Free energy change value (DDG) classified into largely unstable if less than − 0.5 kcal/mol, largely stable if more than 0.5 kcal/mol, and neutral if the value lies in between.
Align-GVGD: combines evolutionary conservation and biophysical properties to classify missense mutations from C0 to C65, where C65 indicates the highest likelihood of functional disruption.
MUpro: A score less than 0 means the mutation decreases the protein stability. The smaller the score, the more confident the prediction is. Conversely, a score more than 0 means the mutation increases the protein stability. The bigger the score, the more confident the prediction is.

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