Is BBS9 p.Gln355= (c.1065G>A) pathogenic?

BBS9 p.Gln355= (c.1065G>A) is classified Conflicting classifications of pathogenicity in BBS9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-01-26). Very rare (popmax 8.48e-05%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS9 p.Gln355= (c.1065G>A)?

BBS9 p.Gln355= (c.1065G>A) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS9 p.Gln355= (c.1065G>A) in the general population?

BBS9 p.Gln355= (c.1065G>A) is very rare (popmax 8.48e-05%, 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.Gln355=

c.1065G>A · rs756380526 · VCV1336861

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.95, phastCons 1
Overall
CADD	7.628	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,882 alleles

Overall 6.2e-05% 1/1,613,876 alleles · very rare exomes 1/1,461,618 · genomes 0/152,258 · joint denominator

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.Gln355=
Coding: c.1065G>A
MANE Select: NM_198428
dbSNP: rs756380526
Type: single nucleotide variant
Location: chr7:33336489 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB
Residue 355: 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.Gln355Ter Pathogenic ★★ same residue
BBS9 p.Gln355His Uncertain significance ★ ⚠ same residue
BBS9 p.Gln355Lys Uncertain significance ★ ⚠ same residue
BBS9 c.1329+1738C>T 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

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-gln355 (accessed [today's date]).

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