Is BSND p.Ala186fs (c.556dup) pathogenic?

BSND p.Ala186fs (c.556dup) is classified Pathogenic in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-06). Very rare (popmax 0.00133%, afr); Associated with Bartter disease type 4A.

What condition is associated with BSND p.Ala186fs (c.556dup)?

BSND p.Ala186fs (c.556dup) is associated with Bartter disease type 4A (ClinVar).

How common is BSND p.Ala186fs (c.556dup) in the general population?

BSND p.Ala186fs (c.556dup) is very rare (popmax 0.00133%, afr) (gnomAD).

BSND p.Ala186fs

c.556dup · VCV3767333

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Bartter disease type 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -3.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,060 alleles

Overall 6.84e-05% 1/1,461,760 alleles · very rare

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.Ala186fs
Coding: c.556dup
MANE Select: NM_057176
Type: Duplication
Location: chr1:55008219 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 186: 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

Similar variants

BSND c.157_177+20del Pathogenic/Likely pathogenic ★★ same condition
BSND c.272+1G>T Pathogenic/Likely pathogenic ★★ same condition
BSND p.Arg8Trp Pathogenic/Likely pathogenic ★★ same condition
BSND p.Glu4Ter Pathogenic ★★ same condition
BSND p.Glu88Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Gly10Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
BSND p.Gly47Arg Pathogenic/Likely pathogenic ★★ same condition
BSND p.Ile12Thr 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-ala186fs (accessed [today's date]).

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