Is BBS9 p.Arg75Ter (c.223C>T) pathogenic?

BBS9 p.Arg75Ter (c.223C>T) is classified Pathogenic in BBS9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-06). Very rare (popmax 0.00667%, amr); Associated with BBS9-related disorder.

What condition is associated with BBS9 p.Arg75Ter (c.223C>T)?

BBS9 p.Arg75Ter (c.223C>T) is associated with BBS9-related disorder, Bardet-Biedl syndrome 9, Bardet-Biedl syndrome (ClinVar).

How common is BBS9 p.Arg75Ter (c.223C>T) in the general population?

BBS9 p.Arg75Ter (c.223C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

BBS9 p.Arg75Ter

c.223C>T · rs775081992 · VCV266106

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 0.00667%, amr)

Conditions

BBS9-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 23
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.1, phastCons 0.73
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 0.00667% Admixed American · 4/60,006 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000753% 11/1,461,610 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
Finnishnot grpmax-eligible	0.00313%	31,957
European (non-Finnish)	0.000424%	235,965

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: BBS9
Protein: p.Arg75Ter
Coding: c.223C>T
MANE Select: NM_198428
dbSNP: rs775081992
Type: single nucleotide variant
Location: chr7:33152811 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB
Residue 75: the 'seven-bladed beta-propeller' region

Full BBS9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BBS9-related disorder

Also linked: Bardet-Biedl syndrome 9 Bardet-Biedl syndrome

Similar variants

BBS9 c.1329+1738C>T Likely pathogenic ★★ same condition
BBS9 c.1552+2T>A Likely pathogenic ★★ same condition
BBS9 c.1693+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.1789+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.1789+1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.2299-2A>C Likely pathogenic ★★ same condition
BBS9 c.2521+1G>T Likely pathogenic ★★ same condition
BBS9 c.263+1G>A 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/bbs9-p-arg75ter (accessed [today's date]).

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