Is BSND p.Pro151fs (c.452del) pathogenic?

BSND p.Pro151fs (c.452del) is classified Conflicting classifications of pathogenicity in BSND (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-10-03). Ultra-rare (popmax 0.034%, sas); Associated with Bartter disease type 4A.

What condition is associated with BSND p.Pro151fs (c.452del)?

BSND p.Pro151fs (c.452del) is associated with Bartter disease type 4A (ClinVar).

How common is BSND p.Pro151fs (c.452del) in the general population?

BSND p.Pro151fs (c.452del) is ultra-rare (popmax 0.034%, sas) (gnomAD).

BSND p.Pro151fs

c.452del · rs765135576 · VCV590851

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

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	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.2, phastCons 0.86
Overall
CADD	19.52	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% South Asian · 31/91,086 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00229% 37/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,938
African / African-American	0.00133%	74,924
European (non-Finnish)	0.000424%	236,010

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.Pro151fs
Coding: c.452del
MANE Select: NM_057176
dbSNP: rs765135576
Type: Deletion
Location: chr1:55007174 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 151: 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)

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.273-887_*576del 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

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-pro151fs (accessed [today's date]).

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