# NM_198428.3(BBS9):c.2430del (p.Lys810fs)

https://sugi.bio/variant/bbs9-p-lys810fs

## Summary

**BBS9 p.Lys810fs (c.2430del)** is classified **Likely pathogenic** in BBS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). Associated with Bardet-Biedl syndrome 9.

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

## For patients & families {#patients}

This is a change in the BBS9 gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to Bardet-Biedl syndrome 9.

*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 recessive, Oligogenic |
| Age of onset (of this condition) | Antenatal, Childhood, Infancy, Neonatal |
| Prevalence | 1-9 / 100 000 (Specific population) |
| Diagnostic panels | BBS9 is a diagnostic-grade gene on 17 Genomics England panels |

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

- Retinal dystrophy — Obligate (100%)
- Cone/cone-rod dystrophy — Very frequent (99-80%)
- Obesity — Very frequent (99-80%)
- Childhood-onset truncal obesity — Very frequent (99-80%)
- Neurodevelopmental delay — Very frequent (99-80%)
- Abnormality of the genitourinary system — Frequent (79-30%)
- Hypogonadism — Frequent (79-30%)
- Abnormal oral cavity morphology — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0010208/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [BBS9](https://sugi.bio/atlas/gene/BBS9/) |
| Protein change (HGVS p.) | p.Lys810fs |
| Coding change (HGVS c.) | c.2430del |
| MANE Select transcript | [NM_198428](https://www.ncbi.nlm.nih.gov/nuccore/NM_198428) |
| Variant type | Deletion |
| Location | chr7:33534083-33534083 (GRCh38) |
| ClinVar | [VCV3594583](https://www.ncbi.nlm.nih.gov/clinvar/variation/3594583/) |

**All HGVS expressions:** `NC_000007.13:g.33573697del`, `NC_000007.14:g.33534085del`, `NG_009306.2:g.409842del`, `NM_001033604.2:c.2325del`, `NM_001033605.2:c.2415del`, `NM_001348036.1:c.2430del`, `NM_001348037.3:c.1881del`, `NM_001348038.3:c.2157del`, `NM_001348039.3:c.2052del`, `NM_001348040.3:c.2310del`, `NM_001348041.4:c.2430del`, `NM_001348042.3:c.2295del`, `NM_001348043.3:c.2430del`, `NM_001348044.3:c.1959del`, `NM_001348045.3:c.2064del`, `NM_001348046.3:c.2064del`, `NM_001362679.1:c.2430del`, `NM_014451.4:c.2310del`, `NM_198428.3:c.2430del`, `NR_145411.1:n.2709del`, `NR_145412.1:n.2901del`, `NR_145413.3:n.3063del`

## 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 8.536, GERP 1.83, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.959, pLI 6.7214e-22. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 21 of 23**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion 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}

**BBS9** population constraint: LOEUF 0.959, pLI 6.7214e-22, missense-Z 1.1685. *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):

- **BBS9-related ciliopathy** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 85.41, 63% of residues very-high.

**2 experimental structure(s)** (PDB): [4YD8](https://www.rcsb.org/structure/4YD8), [6XT9](https://www.rcsb.org/structure/6XT9).

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

*Describes the biological roles of BBS9 (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.*


### Pathways affected {#pathways}

BBS9 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [BBSome-mediated cargo-targeting to cilium](https://reactome.org/content/detail/R-HSA-5620922) | curated |

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

**Biological process:** protein localization to cilium.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-04-08.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Fulgent Genetics, Fulgent Genetics | Likely pathogenic | criteria provided, single submitter | clinical testing | 2024-04-08 |

## Associated conditions {#conditions}

[Bardet-Biedl syndrome 9](https://sugi.bio/atlas/disease/bardet-biedl-syndrome-9/).

**Reported phenotype names (ClinVar):** Bardet-Biedl syndrome 9.

## Similar variants {#similar}

Related BBS9 variant pages (same residue, condition, or type): [BBS9 p.Cys104fs](/variant/bbs9-p-cys104fs), [BBS9 p.Glu604fs](/variant/bbs9-p-glu604fs), [BBS9 p.Gly145fs](/variant/bbs9-p-gly145fs), [BBS9 p.Gly43fs](/variant/bbs9-p-gly43fs), [BBS9 p.Ile392fs](/variant/bbs9-p-ile392fs), [BBS9 p.Lys626fs](/variant/bbs9-p-lys626fs), [BBS9 p.Val72fs](/variant/bbs9-p-val72fs), [BBS9 p.Glu765_Leu766delinsVal](/variant/bbs9-p-glu765-leu766delinsval).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 2026-10-14); 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 3594583). 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.*