Is BBS5 p.Val188fs (c.562dup) pathogenic?

BBS5 p.Val188fs (c.562dup) is classified Pathogenic in BBS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-07). Very rare (popmax 0.000137%); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS5 p.Val188fs (c.562dup)?

BBS5 p.Val188fs (c.562dup) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS5 p.Val188fs (c.562dup) in the general population?

BBS5 p.Val188fs (c.562dup) is very rare (popmax 0.000137%) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS5 p.Val188fs

c.562dup · rs1244442256 · VCV2793507

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

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	predicted	premature termination codon in exon 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.46	GERP -3.8, phastCons 0.15

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000137%

Overall 0.000137% 2/1,460,750 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
Remaining individualsnot grpmax-eligible	0.0016%	62,456

Ashkenazi Jewish 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: BBS5
Protein: p.Val188fs
Coding: c.562dup
MANE Select: NM_152384
dbSNP: rs1244442256
Type: Duplication
Location: chr2:169493779 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 1 PDB

Full BBS5 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

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS5 p.Ala19fs Pathogenic ★★ same condition
BBS5 p.Asn102Ter Pathogenic/Likely pathogenic ★★ same condition
BBS5 p.Asn184_Val185insAsn Pathogenic ★ same condition
BBS5 p.Leu4fs Pathogenic ★ same condition
BBS5 p.Val69fs Pathogenic ★ same condition
BBS5 p.Val188Leu Uncertain significance ★ ⚠ same residue
BBS5 c.142+3_142+10dup Likely benign ★ same condition
BBS5 c.258+14dup Benign ★ 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/bbs5-p-val188fs (accessed [today's date]).

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