Is BSND p.Pro182= (c.546C>T) pathogenic?

BSND p.Pro182= (c.546C>T) is classified Likely benign in BSND (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-20). Ultra-rare (popmax 0.0423%, mid); Associated with Bartter disease type 4A.

What condition is associated with BSND p.Pro182= (c.546C>T)?

BSND p.Pro182= (c.546C>T) is associated with Bartter disease type 4A, Bartter syndrome (ClinVar).

How common is BSND p.Pro182= (c.546C>T) in the general population?

BSND p.Pro182= (c.546C>T) is ultra-rare (popmax 0.0423%, mid) (gnomAD).

BSND p.Pro182=

c.546C>T · rs375551000 · VCV1086153

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, mid)

Conditions

Bartter disease type 4A

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 -1.3	GERP -2.7
Overall
CADD	1.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0423% Middle Eastern · 2/4,730 alleles

Filtering AF 0.00871% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00814%

Overall 0.00904% 122/1,349,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0423%	2,365
European (non-Finnish)	0.0103%	9,665
African / African-American	0.00928%	10,780
Remaining individualsnot grpmax-eligible	0.00654%	15,281
Admixed American	0.00599%	16,682
South Asian	0.00347%	28,809

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: BSND
Protein: p.Pro182=
Coding: c.546C>T
MANE Select: NM_057176
dbSNP: rs375551000
Type: single nucleotide variant
Location: chr1:55007270 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 182: a UniProt-annotated variant site (in barts4a); a UniProt-annotated variant site (in barts4a; loss of clcnka and clcnkb channel conductance); a UniProt-annotated variant site (in barts4a; abolishes the preferential sorting at the basolateral membrane domain; no effect on ion conductance); the 'disordered' region

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

Disease context

Bartter disease type 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bartter syndrome

Similar variants

BSND p.Pro182Ser Uncertain significance ⚠ same residue
BSND c.178-2A>C Likely pathogenic ★★ same condition
BSND c.272+1G>T Pathogenic/Likely pathogenic ★★ same condition
BSND p.Arg8Trp Pathogenic/Likely pathogenic ★★ same condition
BSND p.Gln95Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Glu148Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Glu4Ter Pathogenic ★★ same condition
BSND p.Glu88Ter 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/bsnd-p-pro182 (accessed [today's date]).

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