Is BBS9 p.Arg7Pro (c.20G>C) pathogenic?

BBS9 p.Arg7Pro (c.20G>C) is classified Uncertain significance in BBS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely pathogenic (0.98); Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome.

What condition is associated with BBS9 p.Arg7Pro (c.20G>C)?

BBS9 p.Arg7Pro (c.20G>C) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS9 p.Arg7Pro (c.20G>C) in the general population?

BBS9 p.Arg7Pro (c.20G>C) is absent from gnomAD v4.1 (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

What do computational predictors say about BBS9 p.Arg7Pro (c.20G>C)?

AlphaMissense predicts likely pathogenic (score 0.98) — an in-silico prediction, not a clinical call.

BBS9 p.Arg7Pro

c.20G>C · rs746340993 · VCV1047102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.98 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.98	likely pathogenic · top 2% in BBS9
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -15.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 459 kb · p 0.062 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BBS9
Protein: p.Arg7Pro
Coding: c.20G>C
MANE Select: NM_198428
dbSNP: rs746340993
Type: single nucleotide variant
Location: chr7:33146272 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB
Residue 7: 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.Arg7Cys Uncertain significance ★★ ⚠ same residue
BBS9 p.Arg7His Uncertain significance ★★ ⚠ same residue
BBS9 p.Arg7Leu Uncertain significance ★★ ⚠ same residue
BBS9 p.Arg7Ser 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

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-arg7pro (accessed [today's date]).

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