Is BNC2 p.Ala28= (c.84A>T) pathogenic?

BNC2 p.Ala28= (c.84A>T) is classified Benign in BNC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 8.37%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hypotensive disorder.

What condition is associated with BNC2 p.Ala28= (c.84A>T)?

BNC2 p.Ala28= (c.84A>T) is associated with hypotensive disorder (ClinVar).

BNC2 p.Ala28=

Q: How common is BNC2 p.Ala28= (c.84A>T) in the general population?

BNC2 p.Ala28= (c.84A>T) is common (popmax 8.37%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.84A>T · rs76485966 · VCV120243

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 8.37%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hypotensive disorder

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 -2.2	GERP -4.6
Overall
CADD	3.797	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.37% African / African-American · 6,278/75,014 alleles

Filtering AF 8.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.13%

Overall 1.11% 17,873/1,614,074 alleles · common exomes 13,337/1,461,804 · genomes 4,536/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.37%	12
East Asian	8.02%	12
South Asian	3.42%	29
Amishnot grpmax-eligible	2.96%	34
Middle Eastern	2.31%	43
Ashkenazi Jewishnot grpmax-eligible	1.94%	52
Remaining individualsnot grpmax-eligible	1.73%	58
Admixed American	1.18%	85
Finnishnot grpmax-eligible	0.248%	403
European (non-Finnish)	0.185%	540

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: BNC2
Protein: p.Ala28=
Coding: c.84A>T
MANE Select: NM_017637
dbSNP: rs76485966
Type: single nucleotide variant
Location: chr9:16738405 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.10

Full BNC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypotensive disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BNC2 p.Ala923Val Benign/Likely benign ★★ same condition
BNC2 p.Asp930Gly Likely benign ★★ same condition
BNC2 p.Ile974Val Benign ★★ same condition
BNC2 p.Leu414Val Benign ★★ same condition
BNC2 p.Leu826= Benign/Likely benign ★★ same condition
BNC2 p.Phe312= Benign ★★ same condition
BNC2 p.Pro623His Benign/Likely benign ★★ same condition
BNC2 p.Ser173= Benign/Likely benign ★★ 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/bnc2-p-ala28 (accessed [today's date]).

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