Is BSND p.Pro31Ala (c.91C>G) pathogenic?

BSND p.Pro31Ala (c.91C>G) is classified Uncertain significance in BSND (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-09). AlphaMissense: ambiguous (0.53); Very rare (popmax 0.00988%, sas); Associated with Bartter syndrome.

What condition is associated with BSND p.Pro31Ala (c.91C>G)?

BSND p.Pro31Ala (c.91C>G) is associated with Bartter syndrome (ClinVar).

How common is BSND p.Pro31Ala (c.91C>G) in the general population?

BSND p.Pro31Ala (c.91C>G) is very rare (popmax 0.00988%, sas) (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.Pro31Ala (c.91C>G)?

AlphaMissense predicts ambiguous (score 0.53) — an in-silico prediction, not a clinical call.

BSND p.Pro31Ala

c.91C>G · VCV4063926

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.53 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Bartter syndrome

Computational evidence

Protein change
AlphaMissense	0.53	ambiguous
REVEL	0.68	pathogenic-leaning
SaProt	LLR -7.51	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,090 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000558% 9/1,614,122 alleles · very rare

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.Pro31Ala
Coding: c.91C>G
MANE Select: NM_057176
Type: single nucleotide variant
Location: chr1:54999277 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 31: a UniProt-annotated variant site (in barts4a); 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 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 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
BSND p.Gly10Ser 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-pro31ala (accessed [today's date]).

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