Is BBS2 p.Tyr103fs (c.307del) pathogenic?

BBS2 p.Tyr103fs (c.307del) is classified Pathogenic/Likely pathogenic in BBS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00549%, sas); Associated with BBS2-related disorder.

What condition is associated with BBS2 p.Tyr103fs (c.307del)?

BBS2 p.Tyr103fs (c.307del) is associated with BBS2-related disorder, Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Tyr103fs (c.307del) in the general population?

BBS2 p.Tyr103fs (c.307del) is very rare (popmax 0.00549%, sas) (gnomAD).

BBS2 p.Tyr103fs

c.307del · rs753557069 · VCV2735629

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

BBS2-related disorder

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 7.8	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,086 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000342% 5/1,461,862 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.Tyr103fs
Coding: c.307del
MANE Select: NM_031885
dbSNP: rs753557069
Type: Deletion
Location: chr16:56514491 (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

Also linked: Bardet-Biedl syndrome

Similar variants

BBS2 c.472del Pathogenic/Likely pathogenic ★★ same condition
BBS2 c.804+1_804+14del 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

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-tyr103fs (accessed [today's date]).

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