Is BSND p.Ala161Val (c.482C>T) pathogenic?

BSND p.Ala161Val (c.482C>T) is classified Uncertain significance in BSND (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-01-01). AlphaMissense: likely benign (0.1365); Rare (popmax 0.181%, mid); Associated with Bartter disease type 4A.

What condition is associated with BSND p.Ala161Val (c.482C>T)?

BSND p.Ala161Val (c.482C>T) is associated with Bartter disease type 4A, Bartter syndrome (ClinVar).

How common is BSND p.Ala161Val (c.482C>T) in the general population?

BSND p.Ala161Val (c.482C>T) is rare (popmax 0.181%, mid) (gnomAD).

What do computational predictors say about BSND p.Ala161Val (c.482C>T)?

AlphaMissense predicts likely benign (score 0.1365) — an in-silico prediction, not a clinical call.

BSND p.Ala161Val

c.482C>T · rs369618892 · VCV228463

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1365 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bartter disease type 4A

Computational evidence

Protein change
AlphaMissense	0.1365	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -4.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.38, phastCons 0.026
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	14.69	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% Middle Eastern · 11/6,062 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.00198% 32/1,614,060 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.181%	551
African / African-American	0.0107%	9,380
South Asian	0.00768%	13,013
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.00017%	589,960

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.Ala161Val
Coding: c.482C>T
MANE Select: NM_057176
dbSNP: rs369618892
Type: single nucleotide variant
Location: chr1:55007206 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 161: 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

Also linked: Bartter syndrome

Similar variants

BSND p.Ala161= Likely benign ★ 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-ala161val (accessed [today's date]).

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