Is BBS1 p.Ala591= (c.1773G>A) pathogenic?

BBS1 p.Ala591= (c.1773G>A) is classified Likely benign in BBS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0102%, amr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS1 p.Ala591= (c.1773G>A)?

BBS1 p.Ala591= (c.1773G>A) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 1 (ClinVar).

How common is BBS1 p.Ala591= (c.1773G>A) in the general population?

BBS1 p.Ala591= (c.1773G>A) is ultra-rare (popmax 0.0102%, amr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS1 p.Ala591=

c.1773G>A · rs147783319 · VCV697719

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, amr)

Conditions

Bardet-Biedl syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.8	GERP -4.8
Overall
CADD	1.045	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0102% Admixed American · 6/58,898 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00299%

Overall 0.00168% 27/1,604,370 alleles · ultra-rare exomes 19/1,452,162 · genomes 8/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0102%	9,816
African / African-American	0.00535%	18,689
East Asian	0.00225%	44,478
European (non-Finnish)	0.00128%	78,428
South Asian	0.00111%	89,806

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.Ala591=
Coding: c.1773G>A
MANE Select: NM_024649
dbSNP: rs147783319
Type: single nucleotide variant
Location: chr11:66532028 (GRCh38)

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)

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-ala591 (accessed [today's date]).

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