Is BBS2 p.Val687fs (c.2043_2058dup) pathogenic?

BBS2 p.Val687fs (c.20432058dup) is classified Pathogenic in BBS2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-04). Absent from gnomAD; Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Val687fs (c.2043_2058dup)?

BBS2 p.Val687fs (c.2043_2058dup) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 2 (ClinVar).

How common is BBS2 p.Val687fs (c.2043_2058dup) in the general population?

BBS2 p.Val687fs (c.2043_2058dup) is absent from gnomAD (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Val687fs

c.2043_2058dup · rs1555520212 · VCV551970

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (16 of 17, 0 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: BBS2
Protein: p.Val687fs
Coding: c.2043_2058dup
MANE Select: NM_031885
dbSNP: rs1555520212
Type: Duplication
Location: chr16:56485590 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 2

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.Val687Leu 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.Leu62fs Likely pathogenic ★★ same condition
BBS2 p.Thr555fs 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-val687fs (accessed [today's date]).

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