Is BSND p.Pro193Ala (c.577C>G) pathogenic?

BSND p.Pro193Ala (c.577C>G) is classified Uncertain significance in BSND (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-23). AlphaMissense: likely benign (0.3057); Very rare (popmax 0.000339%, nfe); Associated with Bartter syndrome.

What condition is associated with BSND p.Pro193Ala (c.577C>G)?

BSND p.Pro193Ala (c.577C>G) is associated with Bartter syndrome (ClinVar).

How common is BSND p.Pro193Ala (c.577C>G) in the general population?

BSND p.Pro193Ala (c.577C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Bartter syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BSND p.Pro193Ala (c.577C>G)?

AlphaMissense predicts likely benign (score 0.3057) — an in-silico prediction, not a clinical call.

BSND p.Pro193Ala

c.577C>G · VCV4063913

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Bartter syndrome

Computational evidence

Protein change
AlphaMissense	0.3057	likely benign
REVEL	0.457	indeterminate
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	25.5	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 0.000339% European (non-Finnish) · 4/1,180,030 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,050 alleles · very rare exomes 3/1,461,858 · genomes 1/152,192 · joint denominator

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.Pro193Ala
Coding: c.577C>G
MANE Select: NM_057176
Type: single nucleotide variant
Location: chr1:55008242 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 193: 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 syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bartter syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

BSND p.Pro193Leu Uncertain significance ★★ same residue
BSND p.Pro193= 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

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-pro193ala (accessed [today's date]).

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