Is BBS9 p.Ala65= (c.195C>A) pathogenic?

BBS9 p.Ala65= (c.195C>A) is classified Likely benign in BBS9 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-24). Ultra-rare (popmax 0.03%, amr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS9 p.Ala65= (c.195C>A)?

BBS9 p.Ala65= (c.195C>A) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 9 (ClinVar).

How common is BBS9 p.Ala65= (c.195C>A) in the general population?

BBS9 p.Ala65= (c.195C>A) is ultra-rare (popmax 0.03%, amr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS9 p.Ala65=

c.195C>A · rs373063776 · VCV1135979

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

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 -0.72	GERP -4, phastCons 0.041
Overall
CADD	7.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/59,938 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00124% 20/1,613,396 alleles · ultra-rare exomes 19/1,461,718 · genomes 1/151,678 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,330
Remaining individualsnot grpmax-eligible	0.0032%	31,233

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.Ala65=
Coding: c.195C>A
MANE Select: NM_198428
dbSNP: rs373063776
Type: single nucleotide variant
Location: chr7:33152783 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB
Residue 65: the 'seven-bladed beta-propeller' region; an α-helix

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.Ala65Val 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-ala65 (accessed [today's date]).

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