rs1799958

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'. 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. 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.

A;G

This is a very common variant; see text on main rs-page for discussion.