SERPINA1 rs17580: Understanding the Pi*S Allele
The rs17580 variant in the SERPINA1 gene is commonly referred to as the Pi*S allele. It is associated with a mild-to-moderate reduction in the levels of alpha-1 antitrypsin, a protein that protects the lungs and liver from damage.
What each genotype means
Typical alpha-1 antitrypsin levels
This genotype represents the most common form of the SERPINA1 gene, often referred to as the Pi*M allele. Individuals with this profile typically produce normal levels of the alpha-1 antitrypsin protein, which helps protect the lungs from damage.
This is the most common genotype found globally across all ancestral populations.
Carrier of Pi*S variant
You carry one copy of the Pi*S allele, which is associated with a mild reduction in alpha-1 antitrypsin protein levels. While this is generally not considered a cause of severe deficiency on its own, some research suggests it may be associated with an increased risk of lung conditions like COPD, particularly in individuals exposed to tobacco smoke or biomass-burning smoke. Please discuss your respiratory health and any environmental exposures with your clinician.
Carried by a significant portion of the population, particularly in European and Southern European ancestries.
Reduced alpha-1 antitrypsin function
You carry two copies of the Pi*S allele, which is known to result in reduced functionality and lower levels of the alpha-1 antitrypsin protein compared to the common Pi*M allele. This state is associated with a mild-to-moderate deficiency of the protein, which may increase the risk of developing lung disease. It is recommended to discuss these results with a healthcare provider to understand your personal health context and potential risk factors.
This genotype is less common than the heterozygous state and is most frequently observed in populations of European descent.
What is the rs17580 Variant?
The rs17580 variant is a specific single nucleotide polymorphism (SNP) located within the SERPINA1 gene. In the scientific literature, this variant is widely recognized as the Pi*S allele. The SERPINA1 gene is situated on the long arm of chromosome 14 at position 32.13. This gene provides the instructions for producing the alpha-1 antitrypsin (AAT) protein. When a variation like rs17580 occurs, it can lead to changes in the structure or quantity of the AAT protein produced by the body. Because this gene is highly polymorphic, meaning it has many different variations, researchers track specific SNPs like rs17580 to understand how they influence protein function and individual health outcomes. It is one of the most studied variants in the context of AAT deficiency, alongside other well-known variants like the Pi*Z allele.
The Role of the SERPINA1 Gene
The SERPINA1 gene encodes the alpha-1 antitrypsin protein, which is primarily produced in the liver and released into the bloodstream. The main function of AAT is to protect tissues, particularly the lungs, from damage caused by enzymes released by inflammatory cells. Specifically, AAT inhibits an enzyme called neutrophil elastase, which can break down connective tissue if left unchecked. When the SERPINA1 gene carries variants that reduce the production or function of AAT, the lungs may become more susceptible to damage from environmental factors like smoke or pollutants. While the liver is the primary site of production, the protein's protective effects are systemic. Understanding the function of this gene is essential for grasping why certain genetic variants are linked to conditions like chronic obstructive pulmonary disease (COPD) or liver-related health concerns.
Research and Evidence Strength
Research into rs17580 (Pi*S) indicates that it is associated with a mild-to-moderate deficiency of alpha-1 antitrypsin. Compared to the more severe Pi*Z allele, which is linked to significant protein misfolding and deficiency, the Pi*S variant generally results in higher residual levels of functional AAT. The evidence linking this variant to clinical disease is considered limited or mixed in many contexts. While some studies suggest that individuals carrying the Pi*S allele may have an increased risk for pulmonary issues, especially when combined with other environmental or genetic factors, it is not always sufficient on its own to cause severe disease. Current research continues to investigate how this variant interacts with other genetic markers and lifestyle factors to influence long-term health. It is important to note that genetic associations are statistical in nature and do not guarantee the development of any specific medical condition.
Population Frequency
The rs17580 variant is most frequently observed in European populations, with a minor allele frequency typically ranging between 0.02 and 0.05. The frequency of this allele is notably higher in Southern European populations compared to other regions. Because the distribution of this variant is ancestry-specific, its prevalence varies significantly across different global populations. Epidemiological data on this variant is most robust in Western Europe and the United States, while data in other regions remains less comprehensive. Understanding these frequency patterns helps researchers and clinicians contextualize the potential impact of the variant within specific ancestral groups. As with many genetic variants, the presence of the Pi*S allele is a reflection of historical population migration and genetic diversity rather than a universal marker of health status.
What You Can Do With This Information
Information about your genotype for rs17580 is primarily educational and should be viewed as a tool for understanding your genetic makeup rather than a diagnostic result. If you are concerned about your alpha-1 antitrypsin levels or potential risks for lung or liver health, the most appropriate step is to consult with a healthcare professional. A doctor can order clinical blood tests to measure your actual AAT protein levels, which provides a much clearer picture of your health than a genetic test alone. Never use genetic information to make decisions about your health, such as starting or stopping medications, without professional medical guidance. If you have questions about how your genetic results might influence your health management, bring your report to a genetic counselor or your primary care physician to discuss the findings in the context of your overall medical history.
How common is this variant?
The minor allele frequency for rs17580 is approximately 0.02 to 0.05 in European populations, with the highest prevalence observed in Southern Europe.
Frequently asked questions
Is rs17580 the same as the Z allele?
No, rs17580 corresponds to the S allele (Pi*S). The Z allele (Pi*Z) is a different genetic variant that is generally associated with more severe alpha-1 antitrypsin deficiency.
Does having the Pi*S allele mean I have AAT deficiency?
The Pi*S allele is associated with lower levels of alpha-1 antitrypsin, but it is often considered a mild-to-moderate deficiency. A clinical diagnosis of AAT deficiency is typically confirmed through blood tests that measure protein levels and function.
Should I be worried if I have the AT or TT genotype?
Genetic results are statistical associations and not medical diagnoses. If you are concerned about your results, you should discuss them with a healthcare provider who can evaluate your clinical symptoms and order appropriate diagnostic testing.
Can I change my genotype?
No, your genotype is determined at conception and cannot be changed. However, understanding your genetic predispositions can help you and your doctor make informed decisions about lifestyle choices and preventative health screenings.
Sources & further reading
Educational information only, last refreshed 9/21/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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The 'Z' allele (p.Glu366Lys) associated with alpha-1 antitrypsin deficiency.
Rare deficiency null allele (Pi*Null Granite Falls) in SERPINA1 conferring carrier status for severe alpha-1 antitrypsin deficiency.
The Alpha-1-antitrypsin PI*I deficiency missense allele (Arg39Phe) predisposing carriers to reduced serum levels and pulmonary vulnerability.
The classical Pi*Z pathogenic allele in SERPINA1 leading to severe alpha-1 antitrypsin deficiency, lung emphysema, and liver disease.
Known as the S allele (p.Glu288Val), associated with mild alpha-1 antitrypsin deficiency when compounded with Z alleles.
The Z allele (E342K) of the SERPINA1 gene is the most common cause of severe alpha-1 antitrypsin deficiency.