Is BSND p.Val63= (c.189C>T) pathogenic?

BSND p.Val63= (c.189C>T) is classified Benign/Likely benign in BSND (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-27). Rare (popmax 0.957%, mid); Associated with Bartter disease type 4A.

What condition is associated with BSND p.Val63= (c.189C>T)?

BSND p.Val63= (c.189C>T) is associated with Bartter disease type 4A, Bartter syndrome (ClinVar).

How common is BSND p.Val63= (c.189C>T) in the general population?

BSND p.Val63= (c.189C>T) is rare (popmax 0.957%, mid) (gnomAD).

BSND p.Val63=

c.189C>T · rs144505461 · VCV46549

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.957%, 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 -0.35	GERP -2.5, phastCons 0.006
Overall
CADD	0.148	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.957% Middle Eastern · 58/6,062 alleles

Filtering AF 0.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.689%

Overall 0.199% 3,219/1,614,204 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.957%	105
South Asian	0.748%	134
Ashkenazi Jewishnot grpmax-eligible	0.564%	177
Admixed American	0.273%	366
Remaining individualsnot grpmax-eligible	0.27%	370
European (non-Finnish)	0.165%	605
African / African-American	0.0293%	3,412
Finnishnot grpmax-eligible	0.00937%	10,671
East Asian	0.00223%	44,888

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.Val63=
Coding: c.189C>T
MANE Select: NM_057176
dbSNP: rs144505461
Type: single nucleotide variant
Location: chr1:55005033 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 63: a UniProt-annotated variant site (in barts4a); a UniProt-annotated variant site (in barts4a; loss of clcnka and clcnkb channel conductance); the 'regulates channel membrane trafficking and ion conductance' 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.Val63Ile 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-val63 (accessed [today's date]).

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