Is BBS5 p.Thr296= (c.888G>A) pathogenic?

BBS5 p.Thr296= (c.888G>A) is classified Likely benign in BBS5 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-19). Ultra-rare (popmax 0.0164%, mid); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS5 p.Thr296= (c.888G>A)?

BBS5 p.Thr296= (c.888G>A) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS5 p.Thr296= (c.888G>A) in the general population?

BBS5 p.Thr296= (c.888G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS5 p.Thr296=

c.888G>A · rs777702222 · VCV1045268

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -2.8
Overall
CADD	0.618	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000972%

Overall 0.0018% 29/1,612,374 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00401%	24,957
Remaining individualsnot grpmax-eligible	0.0032%	31,218
East Asian	0.00223%	44,872
European (non-Finnish)	0.00178%	56,128
Admixed American	0.00167%	59,960

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.Thr296=
Coding: c.888G>A
MANE Select: NM_152384
dbSNP: rs777702222
Type: single nucleotide variant
Location: chr2:169503166 (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.Thr296Met Uncertain significance ★★ ⚠ same residue
BBS5 c.143-1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-2A>G Likely pathogenic ★★ same condition
BBS5 c.522+3A>G Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.681+1G>T Pathogenic/Likely pathogenic ★★ same condition
BBS5 p.Arg138Cys Likely pathogenic ★★ same condition
BBS5 p.Arg138His 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/bbs5-p-thr296 (accessed [today's date]).

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