Is BBS1 p.Ser246= (c.738C>T) pathogenic?

BBS1 p.Ser246= (c.738C>T) is classified Likely benign in BBS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-02). Very rare (popmax 0.00667%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS1 p.Ser246= (c.738C>T)?

BBS1 p.Ser246= (c.738C>T) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS1 p.Ser246= (c.738C>T) in the general population?

BBS1 p.Ser246= (c.738C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS1 p.Ser246=

c.738C>T · rs775266312 · VCV704966

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.9	GERP -5
Overall
CADD	3.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,922 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00235% 38/1,613,936 alleles · very rare exomes 30/1,461,748 · genomes 8/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,984
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00254%	39,331
Admixed American	0.00167%	59,996

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.Ser246=
Coding: c.738C>T
MANE Select: NM_024649
dbSNP: rs775266312
Type: single nucleotide variant
Location: chr11:66521284 (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

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>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.159+1G>A Likely pathogenic ★★ same condition
BBS1 c.432+1G>A Pathogenic ★★ same condition
BBS1 c.433-2A>G Likely pathogenic ★★ same condition
BBS1 c.47+1G>T 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/bbs1-p-ser246 (accessed [today's date]).

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