Is BSND p.Ile72Phe (c.214A>T) pathogenic?

BSND p.Ile72Phe (c.214A>T) is classified Uncertain significance in BSND (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-14). AlphaMissense: likely benign (0.1025); Absent from gnomAD v4.1; Associated with Bartter syndrome.

What condition is associated with BSND p.Ile72Phe (c.214A>T)?

BSND p.Ile72Phe (c.214A>T) is associated with Bartter syndrome (ClinVar).

How common is BSND p.Ile72Phe (c.214A>T) in the general population?

BSND p.Ile72Phe (c.214A>T) is absent from gnomAD v4.1 (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.Ile72Phe (c.214A>T)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

BSND p.Ile72Phe

c.214A>T · rs1644382614 · VCV990159

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bartter syndrome

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.18	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 0.62	GERP -2.2, phastCons 0.002
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	9.479	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BSND
Protein: p.Ile72Phe
Coding: c.214A>T
MANE Select: NM_057176
dbSNP: rs1644382614
Type: single nucleotide variant
Location: chr1:55005058 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 72: 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 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.Ile72= 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-ile72phe (accessed [today's date]).

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