MPL rs146249964: What Your Genotype Means
The rs146249964 variant is a specific genetic change located in the MPL gene. It is recognized as a founder mutation within the Ashkenazi Jewish population and is associated with the inherited condition known as congenital amegakaryocytic thrombocytopenia (CAMT).
What each genotype means
Typical MPL gene function
This genotype represents the common, wild-type sequence for the MPL gene. Individuals with this profile do not carry the specific founder mutation associated with congenital amegakaryocytic thrombocytopenia (CAMT) at this location.
This is the most common genotype found in the general population across all ancestries.
Carrier of CAMT mutation
This genotype indicates you are a carrier of the c.79+2T>A mutation in the MPL gene. Being a carrier typically does not cause symptoms of congenital amegakaryocytic thrombocytopenia (CAMT), which is an autosomal recessive condition, but you may wish to discuss reproductive carrier screening with a genetic counselor.
This genotype is found in approximately 1 in 75 individuals of Ashkenazi Jewish descent.
Increased risk for CAMT
This genotype indicates the presence of two copies of the c.79+2T>A mutation, which is a known pathogenic variant associated with congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is a rare inherited bone marrow failure syndrome that typically presents as isolated thrombocytopenia at birth and may progress to pancytopenia. Please consult with a medical geneticist or hematologist to discuss these findings and their clinical implications.
This genotype is extremely rare in the general population.
Understanding the Variant and Its Location
The variant rs146249964, also identified in scientific literature as c.79+2T>A, is a genetic alteration situated within the MPL gene on chromosome 1. This specific change occurs at a canonical splice donor site in intron 1. Splice sites are critical regions of DNA that act as instructions for the cell to correctly assemble messenger RNA, which is the template for building proteins. When a mutation occurs at such a precise location, it can disrupt the normal splicing process, potentially leading to the production of a non-functional or truncated protein. Because this variant is located in a region essential for gene expression, it is categorized as a pathogenic variant in clinical databases, meaning it has a well-documented association with specific health outcomes when inherited in certain patterns.
The Role of the MPL Gene
The MPL gene provides instructions for producing the thrombopoietin receptor, often referred to as c-Mpl. This receptor is found on the surface of hematopoietic stem cells and megakaryocytes, which are the precursor cells responsible for producing platelets. Thrombopoietin is the primary hormone that regulates the production of platelets in the bone marrow. By binding to the c-Mpl receptor, thrombopoietin signals these precursor cells to proliferate and mature into functional platelets, which are essential for blood clotting. When the MPL gene is mutated, the receptor may not function correctly, preventing the body from receiving the necessary signals to produce an adequate number of platelets. This disruption is the underlying mechanism for conditions characterized by low platelet counts, such as congenital amegakaryocytic thrombocytopenia.
Research and Clinical Associations
Research has firmly established that rs146249964 is a founder mutation in the Ashkenazi Jewish population. Congenital amegakaryocytic thrombocytopenia (CAMT) is an autosomal recessive disorder, meaning an individual must inherit two copies of a pathogenic mutation—one from each parent—to manifest the condition. In the context of this variant, individuals who are homozygous (carrying two copies) are at risk for developing CAMT, which typically presents in infancy with severe thrombocytopenia and a lack of megakaryocytes in the bone marrow. The evidence for this association is considered strong in clinical genetics, as the variant has been identified in multiple patients diagnosed with the condition. While the variant is well-studied, clinical outcomes can vary, and genetic counseling is recommended for those who identify as carriers to understand their specific reproductive risks.
Population Frequency and Distribution
The frequency of the rs146249964 variant is notably higher in the Ashkenazi Jewish population compared to the general global population. Studies have estimated the carrier frequency for this specific mutation to be approximately 1 in 75 among individuals of Ashkenazi Jewish descent. In contrast, the variant is extremely rare in other global populations. Because it is a recessive condition, being a carrier (having one copy of the variant) generally does not result in symptoms of CAMT. However, the elevated carrier frequency within this specific ancestral group makes it a common focus for carrier screening programs. Understanding these population-specific statistics is vital for accurate genetic risk assessment and for providing context to individuals who receive positive results from genetic testing.
What This Information Means for You
If you have received information regarding your status for rs146249964, it is important to interpret these results within the context of your family history and ancestral background. Being a carrier of this variant does not mean you have the disease, but it does mean you carry a genetic change that could be passed to your children. If both parents are carriers of a pathogenic MPL mutation, there is a 25% chance with each pregnancy that a child will inherit two copies and potentially develop CAMT. This information is intended for educational purposes and should not be used for self-diagnosis. If you are concerned about your carrier status or reproductive risks, you should consult with a certified genetic counselor or a medical professional who can provide personalized guidance based on your specific genetic profile and family history.
How common is this variant?
The rs146249964 variant has an estimated carrier frequency of 1 in 75 in the Ashkenazi Jewish population, while it remains very rare in other global populations.
Frequently asked questions
What is congenital amegakaryocytic thrombocytopenia?
Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited disorder characterized by a low platelet count and a lack of megakaryocytes in the bone marrow. It typically presents in infancy with bleeding issues.
Does being a carrier of rs146249964 mean I have the disease?
No, being a carrier means you have one copy of the variant. Because the condition is autosomal recessive, you generally need two copies of the mutation to manifest the disease.
Why is this variant common in the Ashkenazi Jewish population?
This is due to a 'founder effect,' where a specific genetic mutation becomes more common in a population because it was present in a small group of ancestors who then expanded over time.
Should I get tested for this variant?
Carrier screening is often recommended for individuals of Ashkenazi Jewish descent who are planning a family. You should discuss the benefits and implications of this testing with a genetic counselor.
Sources & further reading
Educational information only, last refreshed 10/2/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs146249964?
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 — $29