Is BBS1 p.Val366Asp (c.1097T>A) pathogenic?

BBS1 p.Val366Asp (c.1097T>A) is classified Pathogenic in BBS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). AlphaMissense: likely benign (0.2848); Very rare (popmax 0.00167%, amr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS1 p.Val366Asp (c.1097T>A)?

BBS1 p.Val366Asp (c.1097T>A) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS1 p.Val366Asp (c.1097T>A) in the general population?

BBS1 p.Val366Asp (c.1097T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

What do computational predictors say about BBS1 p.Val366Asp (c.1097T>A)?

AlphaMissense predicts likely benign (score 0.2848) — an in-silico prediction, not a clinical call.

BBS1 p.Val366Asp

c.1097T>A · rs2495780320 · VCV2137160

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.2848	likely benign ⚠ discordant with ClinVar
REVEL	0.663	pathogenic-leaning
SaProt	LLR -14.33	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.059 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,024 alleles

Overall 6.84e-05% 1/1,461,006 alleles · very rare

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.Val366Asp
Coding: c.1097T>A
MANE Select: NM_024649
dbSNP: rs2495780320
Type: single nucleotide variant
Location: chr11:66523869 (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 p.Val366Leu 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>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

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-val366asp (accessed [today's date]).

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