Is BBS9 p.Pro330fs (c.987del) pathogenic?

BBS9 p.Pro330fs (c.987del) is classified Pathogenic in BBS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-03). Very rare (popmax 0.000339%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS9 p.Pro330fs (c.987del)?

BBS9 p.Pro330fs (c.987del) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS9 p.Pro330fs (c.987del) in the general population?

BBS9 p.Pro330fs (c.987del) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS9 p.Pro330fs

c.987del · VCV3644313

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Bardet-Biedl syndrome

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 9 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.78	GERP -3.8

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,718 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,368 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BBS9
Protein: p.Pro330fs
Coding: c.987del
MANE Select: NM_198428
Type: Deletion
Location: chr7:33273926 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB
Residue 330: the 'seven-bladed beta-propeller' region; a β-strand

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

Disease context

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

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS9 p.Pro330Leu Uncertain significance ★ ⚠ same residue
BBS9 p.Pro330= Likely benign ★ same residue
BBS9 c.1277_1280delAAGC Pathogenic/Likely pathogenic ★★ same condition
BBS9 p.Asp284_Trp285insTer Pathogenic/Likely pathogenic ★★ same condition
BBS9 p.Cys104fs Pathogenic/Likely pathogenic ★★ same condition
BBS9 p.Glu604fs Pathogenic/Likely pathogenic ★★ same condition
BBS9 p.Gly145fs Pathogenic ★★ same condition
BBS9 p.Ile392fs 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/bbs9-p-pro330fs (accessed [today's date]).

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