Is BBS1 p.Ile147= (c.441C>T) pathogenic?

BBS1 p.Ile147= (c.441C>T) is classified Conflicting classifications of pathogenicity in BBS1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0439%, sas); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS1 p.Ile147= (c.441C>T)?

BBS1 p.Ile147= (c.441C>T) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 1 (ClinVar).

How common is BBS1 p.Ile147= (c.441C>T) in the general population?

BBS1 p.Ile147= (c.441C>T) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS1 p.Ile147=

c.441C>T · rs544997496 · VCV879531

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

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 -5.2	GERP -4.5
Overall
CADD	0.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% South Asian · 40/91,080 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00291% 47/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0048%	20,837
East Asian	0.00446%	22,445
Admixed American	0.00167%	60,002
African / African-American	0.00133%	75,006

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: BBS1
Protein: p.Ile147=
Coding: c.441C>T
MANE Select: NM_024649
dbSNP: rs544997496
Type: single nucleotide variant
Location: chr11:66515548 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 1 PDB

Full BBS1 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

Also linked: Bardet-Biedl syndrome 1

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS1 c.1110+3G>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.1111-2A>G Likely pathogenic ★★ same condition
BBS1 c.1181-9C>G Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.124+1G>A Pathogenic ★★ same condition
BBS1 c.124+1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.159+1G>A Likely pathogenic ★★ same condition
BBS1 c.1608+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.432+1G>A 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/bbs1-p-ile147 (accessed [today's date]).

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