Is BBS9 p.Pro181Ser (c.541C>T) pathogenic?

BBS9 p.Pro181Ser (c.541C>T) is classified Uncertain significance in BBS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). AlphaMissense: likely pathogenic (0.6627); Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome 9.

What condition is associated with BBS9 p.Pro181Ser (c.541C>T)?

BBS9 p.Pro181Ser (c.541C>T) is associated with Bardet-Biedl syndrome 9 (ClinVar).

How common is BBS9 p.Pro181Ser (c.541C>T) in the general population?

BBS9 p.Pro181Ser (c.541C>T) 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.Pro181Ser (c.541C>T)?

AlphaMissense predicts likely pathogenic (score 0.6627) — an in-silico prediction, not a clinical call.

BBS9 p.Pro181Ser

c.541C>T · VCV3594536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6627 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,898)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome 9

Computational evidence

Protein change
AlphaMissense	0.6627	likely pathogenic
REVEL	0.815	moderately pathogenic-leaning
SaProt	LLR -12.67	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 459 kb · p 0.062 · regional, not allelic
Overall
CADD	27.2	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

No allele count reported in gnomAD v4.1 (AN 1,613,898). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BBS9
Protein: p.Pro181Ser
Coding: c.541C>T
MANE Select: NM_198428
Type: single nucleotide variant
Location: chr7:33257334 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB
Residue 181: the 'seven-bladed beta-propeller' region

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

Disease context

Bardet-Biedl syndrome 9 — 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.Pro181Arg Pathogenic same residue
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.263+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.442+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-pro181ser (accessed [today's date]).

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