# NM_152384.3(BBS5):c.39C>G (p.Val13=)

https://sugi.bio/variant/bbs5-p-val13

## Summary

**BBS5 p.Val13= (c.39C>G)** is classified **Benign** in BBS5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 14.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Bardet-Biedl syndrome.

**At a glance:** Benign · review: Multiple submitters · rsID rs10188609 · 5 submitters · 1 linked condition · common (popmax 14.5%, afr) — too common for a highly-penetrant pathogenic allele

## For patients & families {#patients}

This is a change in the BBS5 gene that is classified as benign — not considered disease-causing, submitted by 5 submitters, and is linked to Bardet-Biedl 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 recessive, Oligogenic |
| Age of onset (of this condition) | Antenatal, Childhood, Infancy, Neonatal |
| Prevalence | 1-9 / 100 000 (Specific population) |
| Clinical trials | 18 registered for this condition — see ClinicalTrials.gov |
| Diagnostic panels | BBS5 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/0006866/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [BBS5](https://sugi.bio/atlas/gene/BBS5/) |
| Protein change (HGVS p.) | p.Val13= |
| Coding change (HGVS c.) | c.39C>G |
| MANE Select transcript | [NM_152384](https://www.ncbi.nlm.nih.gov/nuccore/NM_152384) |
| dbSNP | [rs10188609](https://www.ncbi.nlm.nih.gov/snp/rs10188609/) |
| Variant type | single nucleotide variant |
| Location | chr2:169479592-169479592 (GRCh38) |
| ClinVar | [VCV262636](https://www.ncbi.nlm.nih.gov/clinvar/variation/262636/) |

**All HGVS expressions:** `NC_000002.11:g.170336102C>G`, `NC_000002.12:g.169479592C>G`, `NG_011567.1:g.5097C>G`, `NM_152384.3:c.39C>G`

## Computational & population evidence {#evidence}

**Concordance:** Evidence sources **disagree** — common (popmax 14.5%, afr) — too common for a highly-penetrant pathogenic allele.

- **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 1.914, GERP 1.73, phastCons 1 — weakly conserved position
- CADD: **PHRED 14.72**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.54 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **14.5%** (afr) · FAF95 14.3% · FAF99 14.2% · 10,916/75,034 in the highest group · 12,098/1,614,132 alleles overall — common (popmax 14.5%, afr) — too common for a highly-penetrant pathogenic allele.

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 14.5% | 7 |
| Remaining individuals (not grpmax-eligible) | 0.859% | 116 |
| Admixed American | 0.828% | 121 |
| Middle Eastern | 0.33% | 303 |
| South Asian | 0.0176% | 5,693 |
| European (non-Finnish) | 0.00932% | 10,727 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00338% | 29,606 |
| East Asian | 0.00223% | 44,860 |

*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}

**BBS5** population constraint: LOEUF 0.884, pLI 0.00025273, missense-Z 1.0111; 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):

- **BBS5-related ciliopathy** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 88.87, 73% of residues very-high.

**1 experimental structure(s)** (PDB): [6XTB](https://www.rcsb.org/structure/6XTB).

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

*Describes the biological roles of BBS5 (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:** BBS5's established molecular role includes phosphatidylinositol-3-phosphate binding.


### Pathways affected {#pathways}

BBS5 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}

**Molecular function:** phosphatidylinositol-3-phosphate binding, RNA polymerase II-specific DNA-binding transcription factor binding.

**Biological process:** cilium assembly.

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-02-04.

**Submitter consensus:** unanimous (4/4 Benign).

**Submission history:** 12 submissions (2023–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Dr. Peter K. Rogan Lab, Western University |  | no classification provided | in vitro |  |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-02-04 |
| PreventionGenetics, part of Exact Sciences | Benign | criteria provided, single submitter | clinical testing |  |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |
| Mayo Clinic Laboratories, Mayo Clinic | Benign | criteria provided, single submitter | clinical testing | 2023-04-03 |

## Associated conditions {#conditions}

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

**Reported phenotype names (ClinVar):** Bardet-Biedl syndrome, not specified, not provided, Ovarian serous cystadenocarcinoma, Malignant tumor of esophagus, Gastric cancer, Thyroid cancer, nonmedullary, 1, Uterine corpus endometrial carcinoma, Sarcoma, none provided.

## Similar variants {#similar}

Related BBS5 variant pages (same residue, condition, or type): [BBS5 c.143-1G>C](/variant/bbs5-c-143-minus-1g-c), [BBS5 c.209-1G>A](/variant/bbs5-c-209-minus-1g-a), [BBS5 c.209-2A>G](/variant/bbs5-c-209-minus-2a-g), [BBS5 c.522+3A>G](/variant/bbs5-c-522-plus-3a-g), [BBS5 c.681+1G>T](/variant/bbs5-c-681-plus-1g-t), [BBS5 p.Arg138Cys](/variant/bbs5-p-arg138cys), [BBS5 p.Arg138His](/variant/bbs5-p-arg138his), [BBS5 p.Arg89Ter](/variant/bbs5-p-arg89ter).

### 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 262636). 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.*