||Considered to be a 'susceptibility' variant by some for SCAD; see text
||common in clinvar
aka c.625G>A (p.Gly209Ser or G209S)
In brief: ethylmalonic aciduria and SCAD deficiency have been reported to be due to this variant (especially when found in compound heterozygotes), but it's a very common variant and there are 100 year olds who show no signs of the disorder, so it's likely that this variant is necessary but not sufficient to bring about a disease condition ... and the other pre-disposing factors are unclear.
In more detail: This variant was initially reported in 2011 in a few patients with ethylmalonic aciduria and SCAD deficiency, and it was termed a 'susceptibility variant'.[PMID 11134486] Compound heterozygosity for R107C and G209S were described in 2008 as disease causing in Ashkenazi Jewish patients with SCAD, albeit with reduced penetrance depending on additional (unknown) factors.[PMID 18054510] Clearly, though, the frequency of the G209S variant is much higher in the general population than would be expected for a pathogenic mutation; the rs1799958(A) allele frequency is around 20-25% in many Caucasian populations. Furthermore, in a study of Ashkenazi centenarians, 5 of 44 such individuals studied were homozygous for G209S (MAF = 36.4%) and they didn't carry any other missense variants in the ACADS gene, so carrying this variant doesn't lead to reduced longevity in any obvious way.[PMID 25333069]
[PMID 19470168] NPAS2 and PER2 are linked to risk factors of the metabolic syndrome.
[PMID 20180986] CLOCK is suggested to associate with comorbid alcohol use and depressive disorders.