Is BBS2 p.Pro85fs (c.254del) pathogenic?

BBS2 p.Pro85fs (c.254del) is classified Likely pathogenic in BBS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). Very rare (popmax 0.00267%, afr); Associated with Bardet-Biedl syndrome 2.

What condition is associated with BBS2 p.Pro85fs (c.254del)?

BBS2 p.Pro85fs (c.254del) is associated with Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Pro85fs (c.254del) in the general population?

BBS2 p.Pro85fs (c.254del) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Pro85fs

c.254del · VCV3580932

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 -0.09	GERP -3.3, phastCons 0.012
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,230 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.Pro85fs
Coding: c.254del
MANE Select: NM_031885
Type: Deletion
Location: chr16:56514544 (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-pro85fs (accessed [today's date]).

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