Is BBS1 c.159+2del pathogenic?

BBS1 c.159+2del is classified Likely pathogenic in BBS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-02-29). Very rare (popmax 0.00333%, amr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS1 c.159+2del?

BBS1 c.159+2del is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 1 (ClinVar).

How common is BBS1 c.159+2del in the general population?

BBS1 c.159+2del is very rare (popmax 0.00333%, amr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS1 c.159+2del

rs1348187150 · VCV1513499

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Non-coding constraint	Z -0.64	1 kb window · o/e 1.06 · regional · uncalibrated

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,882 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: BBS1
Coding: c.159+2del
MANE Select: NM_024649
dbSNP: rs1348187150
Type: Deletion
Location: chr11:66511241 (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

Also linked: Bardet-Biedl syndrome 1

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS1 c.724-8_726del Pathogenic/Likely pathogenic ★★ same condition
BBS1 p.Ala142fs Likely pathogenic ★★ same condition
BBS1 p.Cys40fs Pathogenic ★★ same condition
BBS1 p.Leu251fs Pathogenic/Likely pathogenic ★★ same condition
BBS1 p.Leu505fs Pathogenic ★★ same condition
BBS1 p.Leu522fs Pathogenic/Likely pathogenic ★★ same condition
BBS1 p.Leu539fs Pathogenic/Likely pathogenic ★★ same condition
BBS1 p.Leu75fs 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-c-159-plus-2del (accessed [today's date]).

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