Is BBS2 p.Leu62fs (c.184dup) pathogenic?

BBS2 p.Leu62fs (c.184dup) is classified Likely pathogenic in BBS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-24). Ultra-rare (gnomAD MAF 2.141e-06); Associated with Bardet-Biedl syndrome 2.

What condition is associated with BBS2 p.Leu62fs (c.184dup)?

BBS2 p.Leu62fs (c.184dup) is associated with Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Leu62fs (c.184dup) in the general population?

BBS2 p.Leu62fs (c.184dup) is ultra-rare (gnomAD MAF 2.141e-06) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Leu62fs

c.184dup · rs1281259093 · VCV2680021

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 2.141e-06)

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 2 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000214% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: BBS2
Protein: p.Leu62fs
Coding: c.184dup
MANE Select: NM_031885
dbSNP: rs1281259093
Type: Duplication
Location: chr16:56514613 (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 p.Leu62Val Uncertain significance ★★ ⚠ same residue
BBS2 p.Ala136fs Likely pathogenic ★★ same condition
BBS2 p.Ala615fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Arg403fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Asn663Ter Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Leu367fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Thr555fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Val94fs 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-leu62fs (accessed [today's date]).

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