Is BBS9 p.Ser637= (c.1911G>A) pathogenic?

BBS9 p.Ser637= (c.1911G>A) is classified Uncertain significance in BBS9 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-31). Ultra-rare (popmax 0.0189%, mid); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS9 p.Ser637= (c.1911G>A)?

BBS9 p.Ser637= (c.1911G>A) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 9 (ClinVar).

How common is BBS9 p.Ser637= (c.1911G>A) in the general population?

BBS9 p.Ser637= (c.1911G>A) is ultra-rare (popmax 0.0189%, mid) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS9 p.Ser637=

c.1911G>A · rs138454676 · VCV647266

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0189%, mid)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.045	moderately benign-leaning
Splicing
SpliceAI	Δ0.50	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.12	GERP -0.2, phastCons 0.78
Overall
CADD	18.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0189% Middle Eastern · 1/5,290 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00186% 30/1,612,326 alleles · ultra-rare exomes 29/1,460,440 · genomes 1/151,886 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0189%	5,290
Remaining individualsnot grpmax-eligible	0.00321%	31,184
European (non-Finnish)	0.00212%	47,193
Admixed American	0.00167%	59,938
South Asian	0.0011%	90,922

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.Ser637=
Coding: c.1911G>A
MANE Select: NM_198428
dbSNP: rs138454676
Type: single nucleotide variant
Location: chr7:33383787 (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 — 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 p.Ser637Leu 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
BBS9 c.2299-2A>C Likely pathogenic ★★ same condition
BBS9 c.2521+1G>T 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-ser637 (accessed [today's date]).

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