Is BBS5 p.Arg89Ter (c.265C>T) pathogenic?

BBS5 p.Arg89Ter (c.265C>T) is classified Pathogenic in BBS5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-23). Very rare (popmax 0.00223%, eas); Associated with Bardet-Biedl syndrome 5.

What condition is associated with BBS5 p.Arg89Ter (c.265C>T)?

BBS5 p.Arg89Ter (c.265C>T) is associated with Bardet-Biedl syndrome 5, Bardet-Biedl syndrome (ClinVar).

How common is BBS5 p.Arg89Ter (c.265C>T) in the general population?

BBS5 p.Arg89Ter (c.265C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS5 p.Arg89Ter

c.265C>T · rs772757329 · VCV531823

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Bardet-Biedl syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 12
Splicing
SpliceAI	Δ0.23	acceptor loss, 6 bp away · masked 0 · deltas
Pangolin	Δ0.28	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.2	GERP 1.6, phastCons 1
Overall
CADD	40.0	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 0.00223% East Asian · 1/44,818 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000992% 16/1,613,378 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,818
Remaining individualsnot grpmax-eligible	0.0016%	62,462
African / African-American	0.00134%	74,870
European (non-Finnish)	0.0011%	90,743

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.Arg89Ter
Coding: c.265C>T
MANE Select: NM_152384
dbSNP: rs772757329
Type: single nucleotide variant
Location: chr2:169487993 (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 5 — 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

BBS5 p.Arg89Gln 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-arg89ter (accessed [today's date]).

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