Is BBS2 p.Arg403fs (c.1206dup) pathogenic?

BBS2 p.Arg403fs (c.1206dup) is classified Pathogenic/Likely pathogenic in BBS2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-22). Very rare (popmax 0.0011%, sas); Associated with Bardet-Biedl syndrome 2.

What condition is associated with BBS2 p.Arg403fs (c.1206dup)?

BBS2 p.Arg403fs (c.1206dup) is associated with Bardet-Biedl syndrome 2, Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Arg403fs (c.1206dup) in the general population?

BBS2 p.Arg403fs (c.1206dup) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Arg403fs

c.1206dup · rs1964267396 · VCV928684

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 10 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.38	GERP -2.3, phastCons 0.001

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Overall 0.000205% 3/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,252
South Asiangrpmax	0.0011%	91,068

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg403fs
Coding: c.1206dup
MANE Select: NM_031885
dbSNP: rs1964267396
Type: Duplication
Location: chr16:56501371 (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: Bardet-Biedl syndrome

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.Arg403His Uncertain significance ★★ ⚠ same residue
BBS2 p.Arg403Leu Uncertain significance ★★ ⚠ same residue
BBS2 p.Arg403= Likely benign ★★ same residue
BBS2 p.Arg403Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BBS2 p.Arg403Pro Uncertain significance ★ ⚠ same residue
BBS2 p.Ala136fs Likely pathogenic ★★ same condition
BBS2 p.Ala615fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Asn663Ter 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-arg403fs (accessed [today's date]).

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