Is BBS1 p.Ser243Arg (c.729C>A) pathogenic?

BBS1 p.Ser243Arg (c.729C>A) is classified Uncertain significance in BBS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: likely benign (0.159); Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome.

What condition is associated with BBS1 p.Ser243Arg (c.729C>A)?

BBS1 p.Ser243Arg (c.729C>A) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS1 p.Ser243Arg (c.729C>A) in the general population?

BBS1 p.Ser243Arg (c.729C>A) 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 BBS1 p.Ser243Arg (c.729C>A)?

AlphaMissense predicts likely benign (score 0.159) — an in-silico prediction, not a clinical call.

BBS1 p.Ser243Arg

c.729C>A · rs1180861221 · VCV1398377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.159	likely benign
REVEL	0.405	indeterminate
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -2, phastCons 0.011
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.059 · regional, not allelic
Overall
CADD	6.642	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: BBS1
Protein: p.Ser243Arg
Coding: c.729C>A
MANE Select: NM_024649
dbSNP: rs1180861221
Type: single nucleotide variant
Location: chr11:66521275 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 1 PDB

Full BBS1 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

BBS1 p.Ser243= Likely benign ★ same residue
BBS1 c.1110+3G>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.1111-2A>G Likely pathogenic ★★ same condition
BBS1 c.1181-9C>G Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.124+1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.159+1G>A Likely pathogenic ★★ same condition
BBS1 c.432+1G>A Pathogenic ★★ same condition
BBS1 c.433-2A>G 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/bbs1-p-ser243arg (accessed [today's date]).

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