Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk

Table 5 Rare non-synonymous CLU variants identified in Stage III Caribbean Hispanic AD cohort.

Stage III: Caribbean Hispanic AD cohort
Gene location^a	DNA^b	Protein^c	dbSNP	Total number	MAF AD	MAF C	Protein location	PolyPhen (PSIC)	SIFT
Exon 5	c.965T > C	p.P322L		2	0.0022		β-chain	possible (1.96)	tolerated (0.25)
Exon 6	c.991G > A	p.D331N		2	0.0022		β-chain	benign (0.119)	tolerated (0.28)
Exon 7	c.1291G > C	p.E431Q		1	0.0011		β-chain	benign (0.133)	tolerated (0.35)
Exon 7	c.1105A > C	p.N369H*	rs9331936	155	0.08 (84 AD)	0.07 (71 C)	β-chain	possible (1.56)	tolerated (0.00)
Exon 7	c.1138G > A	p.D380N*	rs9331938	35	0.01 (13 AD)	0.02 (22 C)	β-chain	benign(0.32)	tolerated (0.36)
Exon 8	c.1343C > T	p.S448L*	rs13494	27	0.01 (13 AD)	0.01 (14 C)	β-chain	benign(0.73)	tolerated (0.23)
Exon 6	c.1004C > T	p.T335I		1		0.0010	β-chain	benign (1.077)	tolerated (0.64)
Exon 7	c.1153G > A	p.V385I		1		0.0010	β-chain	benign (0.150)	tolerated (0.4)

^aGene location position according to the longest CLU transcript with 9 coding exons [NM_001831.2], ^bNumbering according to CLU mRNA sequence starting at the A of the ATG translation initation codon in the reference sequence [GenBank accesion number NM_001831.2], ^cNumbering according to CLU protein sequence [GenPept accession number NP_001822.2]; MAF = Minor Allele Frequency, calculated upon the minimum number of successful sequences. (Caribbean Hispanic cohort: 926 patient and 974 control alleles), * = 3 non-synonymous variants with intermediate frequencies (MAF = 1-5%) in patients and control individuals. Prediction of pathogenicity of missense mutations was performed using in silico programs PolyPhen (benign/possibly damaging/probably damaging) and SIFT (tolerated/not tolerated).