SERPINA1 rs121908560: Understanding the Null Granite Falls Variant
The rs121908560 variant is a rare genetic change in the SERPINA1 gene, specifically identified as the Null Granite Falls allele. It is associated with carrier status for alpha-1 antitrypsin deficiency, a condition that can affect the lungs and liver.
What each genotype means
Typical alpha-1 antitrypsin levels
This genotype represents the most common, functional version of the SERPINA1 gene, often referred to as the Pi*M background. Individuals with this genotype typically produce normal levels of alpha-1 antitrypsin protein, which helps protect the lungs from inflammation. This result does not indicate the presence of the Null Granite Falls deficiency variant.
This is the most common genotype globally, found in the vast majority of the human population.
Carrier of deficiency variant
This genotype indicates you carry one copy of the rare Null Granite Falls deficiency allele and one functional copy of the SERPINA1 gene. Carriers typically maintain sufficient alpha-1 antitrypsin levels to prevent severe deficiency, but you should discuss this result with a healthcare provider to understand your specific risk profile. This variant is classified as a 'null' allele, meaning it does not produce functional protein from the affected copy.
This specific genotype is extremely rare, with a global frequency estimated at less than 0.0001.
Potential severe deficiency
This genotype indicates that both copies of your SERPINA1 gene carry the Null Granite Falls deficiency variant. Because this is a null allele, it is associated with a lack of functional alpha-1 antitrypsin protein production, which may significantly increase the risk of lung or liver disease. Please consult with a medical professional or a genetic counselor to discuss clinical testing and appropriate health monitoring.
This genotype is exceptionally rare and has not been widely documented in general population studies.
What is the rs121908560 Variant?
The rs121908560 variant is a specific alteration located within the SERPINA1 gene. In genetic research, this variant is recognized as a 'null' allele, often referred to as the Null Granite Falls mutation. A null allele is a genetic change that typically results in the complete absence of a functional protein product from that specific gene copy. Because humans carry two copies of the SERPINA1 gene—one inherited from each parent—the presence of this variant on one chromosome means that the individual produces no alpha-1 antitrypsin protein from that specific allele. This variant is categorized as a rare deficiency allele, meaning it is not one of the common variants typically screened for in general population health panels.
The Role of the SERPINA1 Gene
The SERPINA1 gene provides the blueprint for producing the alpha-1 antitrypsin protein. This protein acts as a serine protease inhibitor, or 'serpin,' which serves as a protective shield for the body's tissues. Its primary job is to regulate the activity of enzymes, particularly neutrophil elastase, which can break down connective tissue if left unchecked. When the body does not produce enough functional alpha-1 antitrypsin, these enzymes can damage delicate structures, such as the air sacs in the lungs. Furthermore, the protein is primarily produced in the liver; therefore, certain mutations that cause the protein to misfold or fail to be secreted can lead to the accumulation of abnormal protein within liver cells, potentially causing liver disease.
Research and Clinical Associations
Research into rs121908560 classifies it as a pathogenic null allele. Clinical evidence indicates that individuals who carry this variant are at risk for alpha-1 antitrypsin deficiency. Because it is a null allele, it does not produce a dysfunctional protein that accumulates in the liver; rather, it results in a lack of protein production from that allele. The clinical significance of carrying this variant depends on the status of the other SERPINA1 allele. If an individual inherits a null allele from one parent and a normal allele from the other, they are considered a carrier. While carriers generally maintain enough protein levels to avoid severe symptoms, the evidence regarding the long-term health implications for carriers is limited and often requires clinical evaluation of total serum alpha-1 antitrypsin levels.
Population Frequency
The rs121908560 variant is extremely rare, with a global population frequency estimated at less than 0.0001. It is often described as a founder allele, meaning it is more likely to be found in specific populations or families where the mutation originated and was passed down through generations. Because of its rarity, it is not typically included in standard commercial genetic testing kits, which usually focus on the more common S and Z alleles associated with alpha-1 antitrypsin deficiency. Its presence is generally identified through targeted sequencing in individuals who have already been diagnosed with low alpha-1 antitrypsin levels or who have a strong family history of the condition.
Managing Your Genetic Information
If you have been informed that you carry the rs121908560 variant, it is important to understand that this information is not a medical diagnosis. Genetic carrier status describes your potential to pass a variant to your children, but it does not necessarily mean you will develop symptoms of alpha-1 antitrypsin deficiency. Because this is a rare variant, you should discuss these results with a healthcare provider or a genetic counselor who can interpret the findings in the context of your personal and family health history. They may recommend a blood test to measure your actual serum alpha-1 antitrypsin levels, which provides a more accurate picture of your current health status than genetic testing alone. Always consult with a clinician before making any decisions regarding your health or medical care.
How common is this variant?
The rs121908560 variant is a rare founder allele with a global frequency of less than 0.0001.
Frequently asked questions
What does it mean to be a carrier of a null allele?
Being a carrier means you have one copy of a gene with a mutation and one normal copy. For SERPINA1, carriers usually produce enough protein to maintain normal function, but they can pass the variant to their children.
Is rs121908560 the same as the Z or S allele?
No, rs121908560 is a distinct, rare null allele. The S and Z alleles are the most common variants associated with alpha-1 antitrypsin deficiency, whereas this variant is much less frequent.
Should I be worried if I have this variant?
Genetic variants are only one piece of the puzzle. You should consult with a healthcare professional to determine if your actual protein levels are within a healthy range and to discuss your specific health risks.
How is alpha-1 antitrypsin deficiency diagnosed?
Diagnosis is typically confirmed through a blood test that measures the concentration of the alpha-1 antitrypsin protein in your serum. Genetic testing can identify the specific variant, but protein levels are the clinical standard for assessment.
Sources & further reading
Educational information only, last refreshed 9/28/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs121908560?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in SERPINA1
The 'Z' allele (p.Glu366Lys) associated with 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.
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.