SERPINA1 rs104894337: Understanding the S Allele
The rs104894337 variant in the SERPINA1 gene, commonly referred to as the S allele, results in a p.Glu288Val amino acid substitution. It is associated with alpha-1 antitrypsin deficiency, a condition that can affect lung and liver health when combined with other specific genetic variants.
What each genotype means
Normal alpha-1 antitrypsin levels
This genotype represents the typical, functional version of the SERPINA1 gene, often referred to as the M allele. Individuals with this profile produce normal levels of the alpha-1 antitrypsin protein, which helps protect lung tissue from enzyme-mediated damage.
This is the most common genotype found in the general population across all ancestries.
S allele carrier
You carry one copy of the S allele (p.Glu288Val), which is associated with a mild reduction in alpha-1 antitrypsin protein levels. While this alone typically does not cause clinical deficiency, you should discuss your status with a clinician, especially if you have a family history of lung or liver disease.
The S allele is carried by approximately 2-4% of individuals in Southern European ancestries, though frequencies vary globally.
S allele homozygote
This genotype results in the production of the S variant protein, which is associated with mild alpha-1 antitrypsin deficiency. While this condition is generally less severe than other deficiency types, it may increase susceptibility to lung or liver issues, particularly if other risk factors like smoking are present; please consult with a healthcare provider for personalized guidance.
This genotype is relatively rare, occurring primarily in populations where the S allele frequency is higher, such as in Southern Europe.
What is the rs104894337 Variant?
The variant rs104894337 is a specific change in the DNA sequence of the SERPINA1 gene. In scientific literature, this is often identified as the S allele, which corresponds to a c.863A>T nucleotide change. This change leads to an amino acid substitution where glutamic acid is replaced by valine at position 288 (p.Glu288Val) in the resulting protein. Because this variant is located within the coding region of the gene, it alters the structure of the protein produced by the body. It is one of the most well-documented variants in the SERPINA1 gene, which has been studied extensively due to its role in protein deficiency. Researchers track this variant to understand how it contributes to the overall function of the alpha-1 antitrypsin protein and how it interacts with other genetic markers to influence health outcomes.
The Role of the SERPINA1 Gene
The SERPINA1 gene provides the blueprint for creating the alpha-1 antitrypsin protein. This protein acts as a serine protease inhibitor, or 'serpin,' which is a fancy way of saying it helps regulate chemical reactions by blocking certain enzymes. One of its most critical jobs is to protect the lungs from an enzyme called neutrophil elastase. Neutrophil elastase is released by white blood cells to fight infections, but if it is not properly controlled by alpha-1 antitrypsin, it can begin to damage healthy lung tissue. The protein is primarily produced in the liver and then travels through the bloodstream to reach various parts of the body. When the SERPINA1 gene contains variants like the S allele, the body may produce less of this protective protein or produce a version that does not function as effectively as the standard version, often referred to as the M allele.
Research and Clinical Associations
Research associates the S allele (rs104894337) with alpha-1 antitrypsin deficiency (AATD). While the S allele alone is generally considered to have a milder impact on protein levels compared to other variants like the Z allele (p.Glu342Lys), it is clinically significant when inherited alongside other variants. For example, individuals who carry both an S allele and a Z allele (an SZ genotype) may have a moderate risk of developing health issues related to AATD, such as pulmonary emphysema or liver disease. It is important to note that the evidence for the S allele's impact is often context-dependent, meaning the clinical outcome is heavily influenced by the other copy of the gene inherited from one's parents. Because AATD is a complex condition, researchers continue to study how these specific genetic combinations interact with environmental factors, such as smoking or viral infections, to influence disease progression.
Population Frequency
The S allele is relatively common in certain populations, particularly among individuals of Southern European ancestry. Studies indicate that the allele frequency for this variant is approximately 2-4% in these groups. Because it is a common variant, many people may carry one copy of the S allele without experiencing significant health issues. However, because it is a known marker for AATD, it is frequently included in genetic screening panels designed to identify individuals who might be at risk for deficiency-related conditions. The prevalence of this variant highlights the importance of understanding genetic diversity, as the frequency of specific alleles can vary significantly depending on geographic and ancestral background. Large-scale sequencing efforts continue to refine these frequency estimates, providing a clearer picture of how widespread this variant is across different global populations.
What This Information Means for You
Knowing your status for the rs104894337 variant provides insight into your genetic makeup, but it is not a medical diagnosis. Genetic variants are only one piece of a much larger puzzle that includes your environment, lifestyle, and other genetic factors. If you have concerns about alpha-1 antitrypsin deficiency or your respiratory and liver health, the most important 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. Never use genetic information to make decisions about your health or to change medications without professional guidance. If you are interested in learning more about your risk, a clinician can order appropriate diagnostic tests, such as serum protein quantification, which provide a direct measurement of your alpha-1 antitrypsin levels.
How common is this variant?
The S allele has an approximate frequency of 2-4% in Southern European ancestries.
Frequently asked questions
Is the S allele the same as the Z allele?
No, the S allele (rs104894337) and the Z allele (rs28929474) are different variants in the SERPINA1 gene. While both are associated with alpha-1 antitrypsin deficiency, they have different effects on protein function and are often discussed together because they can be inherited in combination.
Does having the S allele mean I have a disease?
Not necessarily. Many people carry the S allele without experiencing any health problems. Clinical symptoms of alpha-1 antitrypsin deficiency usually depend on the combination of variants you have and other environmental factors.
How can I get tested for alpha-1 antitrypsin deficiency?
Testing is typically performed by healthcare providers through blood tests that measure the level of alpha-1 antitrypsin protein in your serum. If you are concerned about your risk, speak with your doctor about whether testing is appropriate for you.
Can I change my genotype?
No, your genotype is determined at conception and cannot be changed. However, understanding your genetic profile can help you and your doctor make informed decisions about your health and lifestyle.
Sources & further reading
Educational information only, last refreshed 9/20/2026. 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 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.
The Z allele (E342K) of the SERPINA1 gene is the most common cause of severe alpha-1 antitrypsin deficiency.