Table 1:

Top 25 most observed S protein RBD mutations. Here, BFE change refers to the BFE change for the S protein and human ACE2 complex induced by a single-site S protein RBD mutation. A positive mutation-induced BFE change strengthens the binding between S protein and ACE2, which results in more infectious variants. Counts of antibody disruption represent the number of antibody and S protein complexes disrupted by a specific RBD mutation. Here, an antibody and S protein complex is to be disrupted if its binding affinity is reduced by more than 0.3 kcal/mol.¹⁸ In addition, we calculate the antibody disruption ratio (%), which is the ratio of the number of disrupted antibody and S protein complexes over 130 known complexes. Ranks are computed from 683 observed RBD mutations.

Mutation	Worldwide		BFE change		Antibody disruption
	Count	Rank	Change	Rank	Count	Ratio	Rank
N501Y	744354	1	0.5499	30	24	18.46	160
L452R	259345	2	0.5752	28	39	30.0	98
T478K	239619	3	0.9994	2	2	1.54	557
E484K	84167	4	0.0946	272	38	29.23	104
K417T	37748	5	0.0116	433	37	28.46	107
S477N	32673	6	0.0180	422	0	0.0	650
N439K	16154	7	0.1792	159	11	8.46	272
K417N	8399	8	0.1661	176	53	40.77	61
F490S	5617	9	0.4406	52	51	39.23	67
S494P	5119	10	0.0902	282	62	47.69	46
N440K	3379	11	0.6161	22	0	0.0	645
E484Q	3229	12	0.0057	442	30	23.08	130
L452Q	2858	13	0.9802	3	27	20.77	144
A520S	2727	14	0.1495	199	3	2.31	497
N501T	2054	15	0.4514	48	17	13.08	202
R357K	1973	16	0.1393	208	5	3.85	388
A522S	1959	17	0.1283	221	2	1.54	543
R346K	1686	18	0.1234	229	6	4.62	380
V367F	1395	19	0.1764	161	0	0.0	637
N440S	1361	20	0.1499	197	2	1.54	542
P384L	1155	21	0.2681	105	18	13.85	199
Y449S	1146	22	−0.8112	632	85	65.38	16
D427N	1106	23	−0.1133	558	1	0.77	589
R346S	1037	24	0.0374	386	20	15.38	182
A475V	891	25	0.3069	94	10	7.69	289