FSHB rs74315456: Understanding Reproductive Genetic Variants
The rs74315456 variant is a rare genetic change located within the FSHB gene, which provides instructions for making a subunit of the follicle-stimulating hormone. This variant is associated with severe congenital isolated follicle-stimulating hormone deficiency, a condition that can impact reproductive development and fertility.
What each genotype means
Typical FSHB genetic profile
This is the most common genotype observed in the general population. It is considered the reference sequence for this specific location in the ARSA gene region, and it is not associated with the clinical conditions linked to the rare variant allele.
This is the predominant genotype found in the vast majority of the global population.
Heterozygous carrier status
Individuals with this genotype carry one copy of the common allele and one copy of the rare variant allele. Research indicates this variant is linked to specific clinical conditions, and carriers should consult with a medical professional to understand if this result has any personal health implications.
This genotype is extremely rare, with the variant allele frequency reported at less than 0.00001 in global populations.
Rare variant homozygous profile
This genotype represents the homozygous state for the rare variant allele. This variant has been documented in clinical databases in association with metachromatic leukodystrophy, and individuals with this result should discuss the findings with a genetic counselor or physician to determine clinical relevance.
This genotype is exceptionally rare and is not expected to be found in the general population at any significant frequency.
What is rs74315456 and Where is it Located?
The variant rs74315456 is a single nucleotide polymorphism (SNP) situated within the FSHB gene. This gene is located on chromosome 11 in humans and is responsible for encoding the beta subunit of the follicle-stimulating hormone (FSH). FSH is a critical glycoprotein hormone produced by the pituitary gland that plays a central role in the development and function of the gonads—the ovaries in females and the testes in males. Because this variant occurs within the coding region of the gene, it has the potential to alter the structure or function of the resulting protein. Geneticists track such variants to understand how specific changes in the DNA sequence can lead to variations in biological traits or, in some cases, clinical conditions related to hormone production and reproductive health.
The Role of the FSHB Gene
The FSHB gene is essential for the synthesis of the beta subunit of FSH. Once produced, this subunit combines with an alpha subunit to form the complete, functional FSH hormone. FSH is vital for regulating the reproductive system; in women, it stimulates the growth and maturation of ovarian follicles, while in men, it is necessary for the production of sperm within the testes. Because FSH is so central to these processes, any disruption in the FSHB gene can lead to a deficiency in the hormone. When FSH levels are significantly low or absent, the body may fail to initiate or maintain normal pubertal development and reproductive function. Research into this gene helps scientists understand the complex hormonal signaling pathways that govern human fertility and the development of secondary sexual characteristics.
Research and Clinical Evidence
The evidence linking rs74315456 to clinical outcomes is categorized as limited but significant in the context of reproductive medicine. This variant is recognized as a functional mutation associated with severe congenital isolated follicle-stimulating hormone deficiency. Individuals with this deficiency may experience hypogonadotropic hypogonadism, a condition characterized by low levels of sex hormones due to insufficient stimulation from the pituitary gland. Clinical manifestations can include delayed or absent puberty and, in many cases, azoospermia, which is the absence of sperm in the ejaculate. It is important to note that while this variant is linked to these specific reproductive challenges, the clinical presentation can vary between individuals. Because the evidence is limited, ongoing research is required to fully understand the penetrance and expressivity of this variant across different genetic backgrounds.
Population Frequency
The rs74315456 variant is extremely rare in the general population. According to data from the Genome Aggregation Database (gnomAD), the global allele frequency for this variant is less than 0.00001. This low frequency indicates that the variant is not a common polymorphism found in the general public but is instead a rare genetic occurrence. Because it is so uncommon, it is rarely encountered in large-scale population studies, and its presence is typically identified in clinical settings where individuals are being evaluated for specific reproductive or endocrine disorders. The rarity of this variant underscores the importance of specialized genetic testing for those who may have a family history of unexplained infertility or delayed pubertal development.
Interpreting Your Genetic Information
If you have received information about this variant, it is essential to understand that genetic data is only one piece of a larger health picture. This variant is associated with specific reproductive conditions, but it does not provide a diagnosis on its own. If you are concerned about your reproductive health, fertility, or pubertal development, you should consult with a qualified healthcare provider, such as a reproductive endocrinologist or a genetic counselor. They can help interpret your results in the context of your personal and family medical history. Never use genetic information to make medical decisions or change treatments without professional guidance. A clinician can provide the necessary context, order appropriate diagnostic tests, and discuss potential management options tailored to your specific health needs.
How common is this variant?
The rs74315456 variant is extremely rare, with a global allele frequency of less than 0.00001 according to gnomAD data.
Frequently asked questions
What is FSH deficiency?
FSH deficiency is a condition where the body does not produce enough follicle-stimulating hormone. This can lead to issues with puberty and fertility because the hormone is necessary for normal reproductive development.
Can this variant cause infertility?
Yes, this variant is associated with conditions that can lead to infertility, such as azoospermia or delayed puberty. However, a genetic variant is only one factor, and you should speak with a fertility specialist for a full evaluation.
Is this variant common?
No, this variant is very rare in the general population. It is not a common genetic trait found in most people.
Should I get tested for this variant?
Genetic testing is usually recommended by a doctor if there is a specific clinical reason, such as unexplained infertility or delayed puberty. You should discuss the necessity of testing with a healthcare professional.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This missense variant in the FSHB gene is associated with spermatogenic impairment and abnormal sperm counts.
Promoter-adjacent variant linked to FSHB expression, influencing basal follicle-stimulating hormone levels, menstrual cycle duration, and twinning propensity.
Pathogenic loss-of-function variant causing isolated follicle-stimulating hormone deficiency leading to hypogonadotropic hypogonadism.
Functional promoter variant in FSHB influencing serum FSH concentrations and reproductive lifespan.
Variant in the promoter region of FSHB associated with circulating follicle-stimulating hormone levels, age at menarche, and reproductive lifespan.
Variant in the promoter region of FSHB associated with altered follicle-stimulating hormone levels, timing of menarche, and female reproductive lifespan.