# NM_057176.3(BSND):c.478_484dup (p.Val162fs)

https://sugi.bio/variant/bsnd-p-val162fs

## Summary

**BSND p.Val162fs (c.478_484dup)** is classified **Likely pathogenic** in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). Associated with Bartter syndrome.

**At a glance:** Likely pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the BSND gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to Bartter syndrome.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal dominant, Autosomal recessive, X-linked recessive |
| Age of onset (of this condition) | Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal |
| Prevalence | 1-9 / 1 000 000 (Europe) |
| Clinical trials | 2 registered for this condition — see ClinicalTrials.gov |
| Diagnostic panels | BSND is a diagnostic-grade gene on 6 Genomics England panels |

**Commonly reported features of Bartter syndrome** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Abnormality of metabolism/homeostasis — Very frequent (99-80%)
- Short stature — Very frequent (99-80%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0005893/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [BSND](https://sugi.bio/atlas/gene/BSND/) |
| Protein change (HGVS p.) | p.Val162fs |
| Coding change (HGVS c.) | c.478_484dup |
| MANE Select transcript | [NM_057176](https://www.ncbi.nlm.nih.gov/nuccore/NM_057176) |
| Variant type | Duplication |
| Location | chr1:55007200-55007201 (GRCh38) |
| ClinVar | [VCV4063933](https://www.ncbi.nlm.nih.gov/clinvar/variation/4063933/) |

**All HGVS expressions:** `LRG_1282:g.13270_13276dup`, `LRG_1282t1:c.478_484dup`, `NC_000001.10:g.55472875_55472881dup`, `NC_000001.11:g.55007202_55007208dup`, `NG_008965.2:g.13270_13276dup`, `NM_057176.3:c.478_484dup`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 7.902, GERP 1.4, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 1.03, pLI 0.00065519. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 3 of 4**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no duplication variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**BSND** population constraint: LOEUF 1.03, pLI 0.00065519, missense-Z 1.0448; ClinGen dosage — haploinsufficiency 30, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Bartter disease type 4A** — Definitive (AR)

## Protein context {#protein}

Residue **162** lies in 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).

AlphaFold model confidence (whole protein): pLDDT 53.80, 0% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of BSND (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** BSND's established molecular role includes chloride channel regulator activity. p.Val162fs falls in a UniProt-annotated variant site (in barts4a; abolishes the preferential sorting at the basolateral membrane domain; no effect on ion conductance).


### Pathways affected {#pathways}

BSND participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Stimuli-sensing channels](https://reactome.org/content/detail/R-HSA-2672351) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** chloride channel regulator activity.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-01-06.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Natera, Inc. | Likely pathogenic | criteria provided, single submitter | clinical testing | 2025-01-06 |

## Associated conditions {#conditions}

[Bartter syndrome](https://sugi.bio/atlas/disease/bartter-syndrome/).

**Reported phenotype names (ClinVar):** Bartter syndrome.

## Similar variants {#similar}

Related BSND variant pages (same residue, condition, or type): [BSND p.Val162Met](/variant/bsnd-p-val162met), [BSND p.Ala133fs](/variant/bsnd-p-ala133fs), [BSND p.Val162=](/variant/bsnd-p-val162), [BSND c.178-2A>C](/variant/bsnd-c-178-minus-2a-c), [BSND c.272+1G>T](/variant/bsnd-c-272-plus-1g-t), [BSND p.Arg8Trp](/variant/bsnd-p-arg8trp), [BSND p.Gln95Ter](/variant/bsnd-p-gln95ter), [BSND p.Glu148Ter](/variant/bsnd-p-glu148ter).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 4063933). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*