LRRK2 rs34637584: G2019S and Parkinson’s Risk
One change in the LRRK2 gene can alter the activity of an enzyme involved in cellular signaling—and substantially increase susceptibility to Parkinson’s disease. That change is rs34637584, better known as G2019S. It is classified as a pathogenic variant, although carrying it does not mean Parkinson’s disease will inevitably develop [R].
What makes this variant particularly interesting is the gap between its biological effect and its variable outcomes. Some carriers develop Parkinson’s disease, while others remain unaffected into old age. Researchers study this difference to understand what influences whether the disease appears [R]. You can explore this marker in the free LRRK2 GeneExplorer report.
What Is LRRK2 rs34637584?
LRRK2 stands for leucine-rich repeat kinase 2. The gene provides instructions for a protein also called LRRK2, or dardarin. Part of this protein works as a kinase, an enzyme that adds phosphate groups to other proteins to help regulate cellular activity [R].
At rs34637584, a DNA change from G to A changes the protein’s building block at position 2019:
Glycine, abbreviated G, is replaced by
Serine, abbreviated S.
That is why the variant is called G2019S or p.Gly2019Ser. The name describes the protein change; the DNA alleles are G and A [R]
Laboratory research has demonstrated that G2019S increases LRRK2 kinase activity [R].
What Do GG, AG, and AA Mean?
The A allele corresponds to the G2019S variant.
Genotype | Interpretation |
GG | No G2019S copies detected at this position. |
AG | One G2019S copy. This is the usual carrier genotype associated with substantially increased susceptibility. |
AA | Two G2019S copies. This is very rare. |
Clinical summaries report broadly similar disease features in people with one or two copies. Evidence about the rare AA genotype remains limited, making a simple “double dose, double risk” interpretation inappropriate [R].
How Much Does G2019S Increase Parkinson’s Risk?
The most useful question is how many carriers develop Parkinson’s disease by a particular age. Researchers call this age-dependent penetrance.
Studies have produced different estimates:
Study | Population studied | Carriers developing Parkinson’s by age 80 |
Ashkenazi Jewish family cohort | 26% | |
Online study recruited through the 23andMe Research Cohort | 49% | |
Larger analysis using 23andMe and Fox Insight research data | 24% |
The 2025 study included 8,791 LRRK2 G2019S carriers. Its modeled cumulative incidence by age 80 was 24% among these carriers, compared with 2% among participants carrying neither of the two variants examined: LRRK2 G2019S and GBA1 N409S [R].
This illustrates two points together: G2019S can increase susceptibility, yet many carriers remain unaffected.
Why Do Some Carriers Develop Parkinson’s While Others Do Not?
G2019S provides an unusually informative example of how a significant genetic finding can interact with the rest of someone’s biology.
In the 2025 study, researchers also examined polygenic risk—the combined influence of many other Parkinson’s-associated variants. Higher polygenic risk was associated with greater disease susceptibility and earlier diagnosis, including among G2019S carriers [R].
This helps explain why two people with the same LRRK2 result can have different outcomes. One important variant does not erase the influence of other genetic factors. Age also matters: a carrier who is unaffected at 40 has not reached the same point on the risk curve as someone unaffected at 80. That is why a percentage without an age attached can be misleading.
Can You Carry G2019S Without a Family History?
Yes. LRRK2-associated Parkinson’s disease has reduced penetrance, so a parent can carry the variant without developing the condition. A family history may therefore appear absent even when the variant has passed through generations [R]. For a parent with the AG genotype, each child has a 50% chance of inheriting the A allele [R].
What Should You Do With an A-Allele Result?
An apparent AG or AA result in consumer raw DNA deserves clinical confirmation before it informs health or family decisions.
A genetic counselor or clinician can arrange appropriate testing and discuss the result in the context of age, medical history, and family history. Even a confirmed result cannot specify whether symptoms will develop, when they might begin, or how the condition would progress [R].
Explore LRRK2 in GeneExplorer
LRRK2 G2019S connects a specific DNA change with altered enzyme activity and a measurable difference in disease susceptibility.
Visit the free LRRK2 GeneExplorer entry to explore rs34637584 and the biology behind this important Parkinson’s-related variant.
Comments