SERPINA1 rs11542035: Understanding the PI*I Variant
The rs11542035 variant is a specific genetic change within the SERPINA1 gene, which is responsible for producing the alpha-1 antitrypsin protein. This variant, often referred to as the PI*I allele, is associated with potential reductions in serum protein levels and may influence pulmonary health.
What each genotype means
Typical alpha-1 antitrypsin profile
This genotype represents the most common form of the SERPINA1 gene, often referred to as the PI*M background. Individuals with this profile typically produce normal levels of alpha-1 antitrypsin protein, which helps protect the lungs from inflammation.
This is the most common genotype observed globally across all major ancestral populations.
Carrier of deficiency allele
This genotype indicates you carry one copy of the PI*I (Arg39Phe) variant. Research suggests this variant may be associated with reduced serum levels of alpha-1 antitrypsin, which could theoretically increase vulnerability to pulmonary issues, though the clinical impact is considered limited. Please discuss any respiratory concerns or family history with your healthcare provider.
This genotype is rare, with the minor allele frequency estimated at approximately 0.005 to 0.01 in Southern European populations.
Reduced alpha-1 antitrypsin levels
This genotype indicates you carry two copies of the PI*I (Arg39Phe) variant. This state is associated with reduced serum levels of alpha-1 antitrypsin and potential pulmonary vulnerability. Because the clinical evidence for this specific variant is limited, you should consult with a physician or genetic counselor to interpret these results in the context of your overall health and clinical history.
This genotype is extremely rare in the general population.
What is the rs11542035 Variant?
The rs11542035 variant is a single nucleotide polymorphism (SNP) located within the SERPINA1 gene. In genetic terms, this variant represents a missense mutation where the amino acid arginine is replaced by phenylalanine at position 39 (Arg39Phe). This specific change is categorized within the PI*I allele system. Because the SERPINA1 gene is highly polymorphic, researchers track these specific changes to understand how they alter the structure and function of the resulting protein. While many variants in this gene are well-studied, rs11542035 is considered a less common variant, and its specific impact on protein folding and secretion is a subject of ongoing investigation in clinical genetics.
The Role of the SERPINA1 Gene
The SERPINA1 gene provides the essential instructions for creating alpha-1 antitrypsin (AAT). This protein acts as a serine protease inhibitor, a type of molecule that protects tissues from damage caused by enzymes like neutrophil elastase. Under normal conditions, AAT is produced primarily in the liver and released into the bloodstream, where it travels to the lungs to neutralize enzymes that could otherwise break down healthy lung tissue. When the SERPINA1 gene contains certain variants, the resulting AAT protein may be produced in lower quantities, be unstable, or fail to function correctly. This can lead to a deficiency, which is clinically recognized as a risk factor for conditions such as chronic obstructive pulmonary disease (COPD) and emphysema, as well as potential liver complications.
Research and Evidence Strength
Current research into rs11542035 classifies it as a variant with limited evidence regarding its clinical impact. While the PI*S and PI*Z alleles are the most well-documented causes of alpha-1 antitrypsin deficiency, accounting for the vast majority of clinical cases, rarer variants like PI*I (rs11542035) are studied to determine if they contribute to similar, albeit perhaps milder, physiological effects. Scientific literature suggests that this variant may be associated with reduced serum levels of the AAT protein, which could theoretically increase pulmonary vulnerability. However, because it is rare, large-scale clinical data is not as robust as it is for more common alleles. Researchers continue to use functional assays and structural modeling to better understand how this specific amino acid substitution affects the protein's ability to protect the lungs.
Population Frequency
The prevalence of the rs11542035 variant is relatively low, with a minor allele frequency typically estimated between 0.005 and 0.01 in Southern European populations. Because this variant is not widespread, it is not routinely screened for in standard population-wide genetic testing panels. Its distribution is largely ancestry-specific, meaning it is more likely to be identified in individuals with Southern European heritage compared to other global populations. Geneticists often observe that rare variants like this one are concentrated in specific geographic regions due to founder effects or historical population migration patterns. Understanding these frequency patterns helps researchers determine which populations might benefit most from targeted studies regarding AAT-related health risks.
Interpreting Your Genetic Information
If you have received information about your status for the rs11542035 variant, it is important to remember that genetic markers are only one piece of a complex health puzzle. This variant is associated with potential reductions in AAT levels, but it does not serve as a medical diagnosis for any specific disease. Many factors, including environmental exposures like smoking, lifestyle choices, and other genetic modifiers, play a significant role in lung and liver health. You cannot use this information to self-diagnose or predict future health outcomes with certainty. If you are concerned about your alpha-1 antitrypsin levels or your respiratory health, the most appropriate step is to consult with a healthcare professional or a genetic counselor. They can interpret your results in the context of your personal and family medical history and recommend appropriate clinical testing if necessary.
How common is this variant?
The rs11542035 variant is rare, with a minor allele frequency of approximately 0.005 to 0.01, primarily observed in Southern European populations.
Frequently asked questions
Is rs11542035 the same as the Z allele for AAT deficiency?
No, rs11542035 is a distinct variant known as the PI*I allele. The Z allele is a different, more common, and more clinically significant mutation associated with severe alpha-1 antitrypsin deficiency.
Does having this variant mean I have lung disease?
No, having this variant does not mean you have or will develop lung disease. It is a genetic marker that may influence protein levels, but many other factors determine your actual health status.
Should I get my AAT levels tested?
If you have concerns about your respiratory health or a family history of AAT deficiency, you should discuss testing with your doctor. They can order a blood test to measure your actual alpha-1 antitrypsin protein levels.
Is this variant common in my ancestry?
This variant is most frequently reported in Southern European populations. If your ancestry is from this region, you are statistically more likely to carry it than individuals from other parts of the world.
Sources & further reading
Educational information only, last refreshed 9/27/2026. 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 Pi*S allele of SERPINA1 that causes mild-to-moderate deficiency of alpha-1 antitrypsin.
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.