Is BBS9 p.Arg683fs (c.2045dup) pathogenic?

BBS9 p.Arg683fs (c.2045dup) is classified Pathogenic in BBS9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-07-30). Absent from gnomAD; Associated with Bardet-Biedl syndrome 4.

What condition is associated with BBS9 p.Arg683fs (c.2045dup)?

BBS9 p.Arg683fs (c.2045dup) is associated with Bardet-Biedl syndrome 4, Bardet-Biedl syndrome 9 (ClinVar).

How common is BBS9 p.Arg683fs (c.2045dup) in the general population?

BBS9 p.Arg683fs (c.2045dup) is absent from gnomAD (gnomAD).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

BBS9 p.Arg683fs

c.2045dup · rs587777810 · VCV2658

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Bardet-Biedl syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 19 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	GERP -0.21, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BBS9
Protein: p.Arg683fs
Coding: c.2045dup
MANE Select: NM_198428
dbSNP: rs587777810
Type: Duplication
Location: chr7:33388073 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB

Full BBS9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 9

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS9 c.2115+17dup Likely benign ★★ same condition
BBS9 c.702+15dup Benign/Likely benign ★★ same condition
BBS9 p.Leu227fs Likely pathogenic ★ same condition
BBS9 c.1552+2T>A Likely pathogenic ★★ same condition
BBS9 c.1693+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.1789+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.1789+1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.2299-2A>C 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/bbs9-p-arg683fs (accessed [today's date]).

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