Is HSD11B2 p.Ala196= (c.588G>A) pathogenic?

HSD11B2 p.Ala196= (c.588G>A) is classified Benign/Likely benign in HSD11B2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 28.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with apparent mineralocorticoid excess.

What condition is associated with HSD11B2 p.Ala196= (c.588G>A)?

HSD11B2 p.Ala196= (c.588G>A) is associated with apparent mineralocorticoid excess (ClinVar).

How is Apparent mineralocorticoid excess inherited?

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

HSD11B2 p.Ala196=

Q: How common is HSD11B2 p.Ala196= (c.588G>A) in the general population?

HSD11B2 p.Ala196= (c.588G>A) is common (popmax 28.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.588G>A · rs5480 · VCV36369

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 28.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

apparent mineralocorticoid excess

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6	GERP -5.2
Overall
CADD	0.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.9% African / African-American · 21,653/74,996 alleles

Filtering AF 28.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.4%

Overall 1.57% 25,300/1,614,120 alleles · common exomes 12,867/1,461,864 · genomes 12,433/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	28.9%	3
Admixed American	2.08%	48
Remaining individualsnot grpmax-eligible	2.03%	49
Middle Eastern	1.91%	52
Ashkenazi Jewishnot grpmax-eligible	0.348%	287
European (non-Finnish)	0.0717%	1,395
South Asian	0.067%	1,493
East Asian	0.00668%	14,959
Finnishnot grpmax-eligible	0.00156%	64,014

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: HSD11B2
Protein: p.Ala196=
Coding: c.588G>A
MANE Select: NM_000196
dbSNP: rs5480
Type: single nucleotide variant
Location: chr16:67436066 (GRCh38)
Gene constraint: LOEUF 1.204 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.49

Full HSD11B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

apparent mineralocorticoid excess — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Apparent mineralocorticoid excess (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

HSD11B2 p.Ala196Thr Uncertain significance ★★ ⚠ same residue
HSD11B2 p.Ala196Gly Uncertain significance ★ ⚠ same residue
HSD11B2 p.Ala328Val Likely pathogenic ★★ same condition
HSD11B2 p.Arg208His Pathogenic/Likely pathogenic ★★ same condition
HSD11B2 c.664+14C>T Uncertain significance ★★ same condition
HSD11B2 p.Ala19Val Uncertain significance ★★ ⚠ same condition
HSD11B2 p.Ala389Thr Uncertain significance ★★ ⚠ same condition
HSD11B2 p.Arg147His Uncertain significance ★★ ⚠ 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/hsd11b2-p-ala196 (accessed [today's date]).

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