CYP21A2 rs72552757: 21-Hydroxylase Deficiency Carrier Status
The rs72552757 single nucleotide polymorphism is a rare coding variant located in the CYP21A2 gene. In human genetics, it is cataloged as a pathogenic variant that confers carrier status for 21-hydroxylase deficiency, an autosomal recessive form of congenital adrenal hyperplasia. Individuals carrying one copy of the altered allele are typically asymptomatic carriers who can pass the variant to their biological children.
What each genotype means
Typical 21-hydroxylase function
You carry two reference copies at this genomic position in CYP21A2. You do not carry this specific pathogenic variant associated with 21-hydroxylase deficiency. However, because CYP21A2 has complex pseudogene arrangements and multiple distinct pathogenic variants, this test does not rule out carrier status for other mutations in the gene.
Carried by more than 99% of individuals across all major global populations.
Carrier of 21-hydroxylase deficiency
You carry one copy of the pathogenic missense variant in the CYP21A2 gene, conferring carrier status for autosomal recessive 21-hydroxylase deficiency. As a carrier, you are typically asymptomatic because one functional copy is sufficient for normal adrenal hormone synthesis. If reproductive planning is relevant, carrier screening for your partner can clarify the risk of passing congenital adrenal hyperplasia to offspring.
Found in fewer than 1 in 200 individuals across most ancestral groups, with an overall allele frequency below 0.005 in gnomAD.
Deficient 21-hydroxylase activity
You carry two copies of the pathogenic variant in CYP21A2, which is associated with autosomal recessive 21-hydroxylase deficiency (congenital adrenal hyperplasia). Individuals homozygous for severe or classical CYP21A2 variants typically exhibit impaired cortisol and aldosterone production and require clinical management. Comprehensive molecular analysis and endocrine evaluation are typically used to confirm full gene copy number and phase.
Extremely rare in general populations, occurring in far fewer than 1 in 40,000 individuals.
Genomic Context and the CYP21A2 Gene
The rs72552757 variant is situated within the CYP21A2 gene on chromosome 6. This gene encodes steroid 21-hydroxylase, a member of the cytochrome P450 superfamily of enzymes. The 21-hydroxylase enzyme plays an indispensable role in steroidogenesis, the biological pathway responsible for converting precursor molecules into cortisol and aldosterone within the adrenal cortex. Cortisol helps regulate energy metabolism, immune response, and the body's reaction to stress, while aldosterone maintains essential salt and fluid balance in the kidneys. Variants that alter the coding sequence of CYP21A2 can severely compromise enzyme function. When both copies of the gene carry loss-of-function variants, impaired steroid production leads to congenital adrenal hyperplasia (CAH), which accounts for roughly 95% of all CAH cases according to [MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/21-hydroxylase-deficiency/).
Clinical Significance and Strength of Evidence
In clinical genetics and reproductive screening, rs72552757 is classified as a classic pathogenic variant associated with 21-hydroxylase deficiency. According to [NCBI ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/variation/12179/), missense and loss-of-function alterations at this locus disrupt enzymatic activity. Because 21-hydroxylase deficiency is inherited in an autosomal recessive manner, carrying a single altered allele generally does not cause classic adrenal insufficiency. Instead, it classifies an individual as an asymptomatic carrier. Although current catalog classifications report limited evidence for broad systemic phenotypes in single-allele carriers, extensive clinical documentation established in [GeneReviews](https://www.ncbi.nlm.nih.gov/books/NBK1171/) confirms that inheriting two pathogenic alleles causes classic or non-classic congenital adrenal hyperplasia. Carriers may occasionally exhibit subtle, subclinical alterations in precursor hormone levels, such as 17-hydroxyprogesterone, under physiological stimulation.
Population Frequency and Pseudogene Complexity
According to reference resources including the Genome Aggregation Database (gnomAD), the minor allele frequency of rs72552757 is very low, typically remaining well below 0.005 (<0.5%) across global populations. However, broader carrier rates for any pathogenic variant across the entire CYP21A2 locus are estimated at approximately 1 in 50 to 1 in 70 individuals worldwide, as outlined in [The Journal of Clinical Endocrinology & Metabolism](https://academic.oup.com/jcem/article/104/12/6148/5544511). Analyzing rs72552757 is technically challenging because CYP21A2 shares high sequence homology with an adjacent, non-functional pseudogene known as CYP21A1P. Recombination and unequal crossing-over between these two regions can generate complex deletions and gene conversions, requiring specialized molecular assays to accurately differentiate authentic CYP21A2 variants from homologous pseudogene sequences.
Interpreting Results and Reproductive Considerations
Identifying a variant at rs72552757 provides actionable genetic information primarily relevant to reproductive planning and family counseling. An individual possessing a single altered allele is not diagnosed with congenital adrenal hyperplasia, nor does the presence of a single variant imply that daily hormone supplementation is necessary. Rather, carrier status indicates a 50% probability of passing that variant to offspring. When both reproductive partners are confirmed carriers of a pathogenic CYP21A2 variant, each pregnancy carries a 25% chance of inheriting both variants and being affected by 21-hydroxylase deficiency. Anyone learning of their carrier status should consult a board-certified genetic counselor or a reproductive specialist, who can order comprehensive partner screening and provide guidance on prenatal diagnostic options.
How common is this variant?
The rs72552757 variant is very rare globally, showing a minor allele frequency of less than 0.005 in gnomAD. Overall carrier frequency for any pathogenic CYP21A2 mutation is estimated at approximately 1 in 50 to 1 in 70 individuals in the general population.
Frequently asked questions
Does having the rs72552757 variant mean I have congenital adrenal hyperplasia?
No. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder, meaning an individual must inherit two non-working gene copies to manifest the condition. Individuals with one copy of rs72552757 are typically asymptomatic carriers who maintain sufficient enzyme activity for standard adrenal hormone production.
What is the primary role of the CYP21A2 gene in the human body?
The CYP21A2 gene directs the synthesis of the 21-hydroxylase enzyme, which operates in the adrenal cortex. This enzyme is necessary to convert precursor steroids into cortisol, which governs stress responses and glucose metabolism, and aldosterone, which regulates fluid and electrolyte balance.
Why is testing for CYP21A2 variants technically difficult?
CYP21A2 is located directly next to an inactive pseudogene, CYP21A1P, which shares roughly 98% sequence identity. Standard genotyping microarrays and basic sequencing methods can misidentify sequences between the gene and pseudogene, necessitating specialized clinical assays to confirm true variants.
What should I do if my carrier screening report flags rs72552757?
If your report shows a carrier genotype, the most important step is to discuss the findings with a genetic counselor or your reproductive healthcare team. They can evaluate whether reproductive partner screening is recommended to assess the likelihood of having a child affected by congenital adrenal hyperplasia.
Sources & further reading
Educational information only, last refreshed 9/14/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP21A2
Pathogenic variant (p.Val282Leu) in CYP21A2 associated with non-classic congenital adrenal hyperplasia.
Pathogenic variant associated with non-classic congenital adrenal hyperplasia presenting with hyperandrogenism, oligomenorrhea, and subfertility.
Pathogenic missense variant in CYP21A2 associated with 21-hydroxylase deficiency, a cause of congenital adrenal hyperplasia.
Well-characterized pathogenic missense variant (p.Pro30Leu) causing non-classic congenital adrenal hyperplasia and female hyperandrogenic subfertility.
This variant in the CYP21A2 gene is involved in steroid hormone metabolism and is noted in clinical databases.
This variant is classified as pathogenic and is associated with 21-hydroxylase deficiency.