Is BBS1 p.Val491= (c.1473G>A) pathogenic?

BBS1 p.Val491= (c.1473G>A) is classified Uncertain significance in BBS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-26). Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome 1.

What condition is associated with BBS1 p.Val491= (c.1473G>A)?

BBS1 p.Val491= (c.1473G>A) is associated with Bardet-Biedl syndrome 1 (ClinVar).

How common is BBS1 p.Val491= (c.1473G>A) in the general population?

BBS1 p.Val491= (c.1473G>A) is absent from gnomAD v4.1 (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS1 p.Val491=

c.1473G>A · rs1856699471 · VCV972683

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Bardet-Biedl syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.33	donor gain · deltas
Pangolin	Δ0.43	loss · gain 0.42 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Overall
CADD	19.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BBS1
Protein: p.Val491=
Coding: c.1473G>A
MANE Select: NM_024649
dbSNP: rs1856699471
Type: single nucleotide variant
Location: chr11:66529952 (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 1 — 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 p.Val491Met Uncertain significance ★★ ⚠ same residue
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.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-val491 (accessed [today's date]).

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