Is BSND p.Pro96= (c.288G>A) pathogenic?

BSND p.Pro96= (c.288G>A) is classified Likely benign in BSND (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-19). Very rare (popmax 0.00439%, sas); Associated with Bartter disease type 4A.

What condition is associated with BSND p.Pro96= (c.288G>A)?

BSND p.Pro96= (c.288G>A) is associated with Bartter disease type 4A (ClinVar).

How common is BSND p.Pro96= (c.288G>A) in the general population?

BSND p.Pro96= (c.288G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

BSND p.Pro96=

c.288G>A · rs752911029 · VCV1100449

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 -2.4	GERP -2
Overall
CADD	6.738	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,086 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00242% 39/1,613,962 alleles · very rare exomes 37/1,461,814 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
European (non-Finnish)	0.00271%	36,876
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00133%	74,916

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.Pro96=
Coding: c.288G>A
MANE Select: NM_057176
dbSNP: rs752911029
Type: single nucleotide variant
Location: chr1:55007012 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 96: 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 p.Pro96Leu Uncertain significance ★★ ⚠ same residue
BSND p.Pro96Gln Uncertain significance ⚠ same residue
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-pro96 (accessed [today's date]).

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