Is BBS2 p.Ser286fs (c.856del) pathogenic?

BBS2 p.Ser286fs (c.856del) is classified Likely pathogenic in BBS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-14). Very rare (popmax 8.47e-05%, nfe); Associated with Bardet-Biedl syndrome 2.

What condition is associated with BBS2 p.Ser286fs (c.856del)?

BBS2 p.Ser286fs (c.856del) is associated with Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Ser286fs (c.856del) in the general population?

BBS2 p.Ser286fs (c.856del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Ser286fs

c.856del · rs2543714143 · VCV3239708

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Bardet-Biedl syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,882 alleles · very rare

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: BBS2
Protein: p.Ser286fs
Coding: c.856del
MANE Select: NM_031885
dbSNP: rs2543714143
Type: Deletion
Location: chr16:56502757 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49

Full BBS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 74

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS2 c.472del Pathogenic/Likely pathogenic ★★ same condition
BBS2 c.940+1del Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Arg339fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Asn258fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Asp371fs Likely pathogenic ★★ same condition
BBS2 p.Asp649fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Cys210fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Glu86fs 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/bbs2-p-ser286fs (accessed [today's date]).

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