Is CYP11B1 p.Arg366= (c.1098T>G) pathogenic?

CYP11B1 p.Arg366= (c.1098T>G) is classified Benign/Likely benign in CYP11B1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele; Associated with glucocorticoid-remediable aldosteronism.

What condition is associated with CYP11B1 p.Arg366= (c.1098T>G)?

CYP11B1 p.Arg366= (c.1098T>G) is associated with glucocorticoid-remediable aldosteronism, congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency (ClinVar).

How is Familial hyperaldosteronism type I inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CYP11B1 p.Arg366=

Q: How common is CYP11B1 p.Arg366= (c.1098T>G) in the general population?

CYP11B1 p.Arg366= (c.1098T>G) is common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1098T>G · rs61752769 · VCV362150

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

glucocorticoid-remediable aldosteronism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -2, phastCons 0.004
Overall
CADD	7.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.19% African / African-American · 3,594/69,186 alleles

Filtering AF 5.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5%

Overall 0.482% 7,716/1,599,246 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.19%	19
Middle Eastern	0.748%	134
South Asian	0.663%	151
Admixed American	0.614%	163
Remaining individualsnot grpmax-eligible	0.54%	185
East Asian	0.493%	203
Ashkenazi Jewishnot grpmax-eligible	0.232%	432
European (non-Finnish)	0.208%	480
Finnishnot grpmax-eligible	0.0776%	1,289

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CYP11B1
Protein: p.Arg366=
Coding: c.1098T>G
MANE Select: NM_000497
dbSNP: rs61752769
Type: single nucleotide variant
Location: chr8:142875735 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.10 · 2 PDB
Residue 366: a UniProt-annotated variant site (in ah4; decreases steroid 11-beta-hydroxylase activity); an α-helix

Full CYP11B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glucocorticoid-remediable aldosteronism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

For Familial hyperaldosteronism type I (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CYP11B1 p.Arg366His Uncertain significance ★ ⚠ same residue
CYP11B1 c.396-2A>G Likely pathogenic ★★ same condition
CYP11B1 c.596-2A>T Pathogenic/Likely pathogenic ★★ same condition
CYP11B1 p.Ala306Val Pathogenic/Likely pathogenic ★★ same condition
CYP11B1 p.Arg138Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CYP11B1 p.Arg141Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CYP11B1 p.Arg141Ter Pathogenic ★★ same condition
CYP11B1 p.Arg143Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cyp11b1-p-arg366 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown