VHL rs121913344: Understanding This Rare Genetic Variant
The rs121913344 variant is a rare genetic alteration located within the VHL gene. It is recognized as a pathogenic missense mutation associated with an increased risk of developing von Hippel-Lindau (VHL) disease, a condition characterized by the growth of various tumors and cysts.
What each genotype means
Typical VHL gene profile
This genotype represents the common, wild-type sequence for this position in the VHL gene. It is not associated with the pathogenic Arg167Gln mutation linked to von Hippel-Lindau disease.
This is the most common genotype found in the general population.
Pathogenic variant carrier
This genotype includes one copy of the pathogenic Arg167Gln variant. Because von Hippel-Lindau disease is an autosomal dominant condition, carrying this variant may predispose an individual to hemangioblastomas, pheochromocytomas, and clear cell renal carcinoma. Please consult with a genetic counselor or medical specialist to discuss the clinical implications of this finding.
This specific pathogenic variant is extremely rare in unselected populations.
Homozygous pathogenic variant
This genotype indicates the presence of two copies of the pathogenic Arg167Gln variant. This is associated with a high risk for von Hippel-Lindau disease manifestations, including tumors and cysts in various organ systems. Clinical evaluation by a specialist is strongly recommended to understand your specific health risks.
This genotype is exceptionally rare and is not typically observed in the general population.
What is the rs121913344 Variant?
The rs121913344 variant is a specific change in the DNA sequence of the VHL gene, which is located on the short arm of chromosome 3. In genetic terms, this is a missense mutation, meaning that a single nucleotide change results in the substitution of one amino acid for another in the resulting protein. Specifically, this variant is often identified as p.Arg167Gln, where the amino acid arginine is replaced by glutamine at position 167 of the VHL protein. Because the VHL gene acts as a critical tumor suppressor, alterations in its sequence can disrupt the normal regulation of cell growth and division. This specific variant is categorized as pathogenic, meaning it is known to interfere with the protein's ability to function correctly, thereby predisposing individuals to specific hereditary cancer syndromes.
The Role of the VHL Gene
The VHL gene provides instructions for making a protein that acts as part of a larger complex known as an E3 ubiquitin ligase. This complex is essential for the body's adaptive response to low oxygen levels, or hypoxia. Under normal conditions, the VHL protein helps tag specific proteins for degradation, particularly those that would otherwise trigger blood vessel growth and cell proliferation when oxygen is abundant. When the VHL gene is mutated, the resulting protein may lose its ability to regulate these processes. This leads to the inappropriate accumulation of proteins that promote tumor growth, even when oxygen levels are normal. This mechanism explains why individuals with pathogenic VHL variants are prone to developing vascular tumors, such as hemangioblastomas, as well as other benign or malignant growths in organs like the kidneys, pancreas, and adrenal glands.
Research and Clinical Associations
Scientific research has established a strong link between pathogenic VHL variants and von Hippel-Lindau disease, a multisystem familial cancer syndrome. The p.Arg167Gln mutation is one of the more frequently observed pathogenic variants in clinical cohorts. Studies have shown that carriers of such mutations face an increased risk of developing retinal and central nervous system hemangioblastomas, pheochromocytomas, and clear cell renal carcinoma. While the association between this variant and the disease is well-documented in clinical literature, the specific penetrance—or the likelihood that a carrier will develop symptoms—can vary between individuals. It is important to note that while this variant is a known risk factor, it does not guarantee that an individual will develop all associated conditions. Clinical management for those with such variants typically involves regular, lifelong screening to detect and treat tumors at an early stage.
Population Frequency and Interpretation
The rs121913344 variant is extremely rare in the general, unselected population. Because it is associated with a serious hereditary condition, it is not a common polymorphism found in the general public. Most individuals who carry this variant are identified through clinical genetic testing after a diagnosis of VHL disease or through family screening programs. Because the variant is so rare, it is not typically included in standard direct-to-consumer ancestry or wellness genetic tests. If you have received information about this variant from a clinical laboratory, it is essential to discuss the findings with a genetic counselor or a medical specialist. They can provide context regarding your specific health history and explain what the presence of this variant means for you and your family members.
What You Can and Cannot Do
If you are concerned about your genetic risk for VHL disease, the most important step is to consult with a healthcare professional, such as a clinical geneticist. They can determine if genetic testing is appropriate based on your personal and family medical history. You cannot use this information to self-diagnose or predict the exact timing of any potential health issues. Genetic testing for rare, high-penetrance variants is a medical procedure that requires professional interpretation to ensure accuracy and to provide appropriate follow-up care. If you have been identified as a carrier of a VHL variant, your doctor will likely recommend a personalized surveillance plan, which may include regular imaging of the brain, spine, and abdomen. Always rely on guidance from your medical team rather than online information when making decisions about your health and screening schedule.
How common is this variant?
The rs121913344 variant is extremely rare in unselected populations, as it is a pathogenic mutation associated with a specific hereditary disease.
Frequently asked questions
What is von Hippel-Lindau disease?
Von Hippel-Lindau (VHL) disease is a rare, inherited disorder that causes the growth of tumors and cysts in various parts of the body. These growths can occur in the brain, spinal cord, eyes, kidneys, and adrenal glands.
Is rs121913344 the same as p.Arg167Gln?
Yes, rs121913344 is the identifier for the genetic variant, while p.Arg167Gln describes the specific change in the protein structure. Both terms refer to the same underlying genetic alteration.
Should I get tested for this variant?
Genetic testing for VHL is generally recommended only for individuals with a personal or family history of VHL-associated tumors. You should discuss your family history with a doctor or genetic counselor to see if testing is appropriate for you.
Can I change my risk if I have this variant?
You cannot change your genetic sequence, but you can manage your health risks. If you carry a pathogenic VHL variant, regular medical surveillance is the standard of care to detect and treat tumors early.
Sources & further reading
Educational information only, last refreshed 9/29/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A pathogenic variant in the VHL gene causing Von Hippel-Lindau disease.
Predisposes to von Hippel-Lindau disease, increasing the lifetime risk of clear cell renal carcinomas and pheochromocytomas.
A missense variant (p.Leu89Pro) in the VHL gene associated with hereditary cancer predisposition.