Is BBS12 p.Cys464fs (c.1392_1395del) pathogenic?

BBS12 p.Cys464fs (c.13921395del) is classified Pathogenic in BBS12 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-11-21). Very rare (popmax 8.47e-05%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS12 p.Cys464fs (c.1392_1395del)?

BBS12 p.Cys464fs (c.1392_1395del) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 1 (ClinVar).

How common is BBS12 p.Cys464fs (c.1392_1395del) in the general population?

BBS12 p.Cys464fs (c.1392_1395del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS12 p.Cys464fs

c.1392_1395del · rs2150737232 · VCV1440165

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.25	GERP -0.93

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,886 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: BBS12
Protein: p.Cys464fs
Coding: c.1392_1395del
MANE Select: NM_152618
dbSNP: rs2150737232
Type: Microsatellite
Location: chr4:122743282 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.92

Full BBS12 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

BBS12 p.Cys464Arg Uncertain significance ★★ ⚠ same residue
BBS12 p.Asp687fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.His260fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Pro632fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Ser196_Tyr197insTer Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Tyr640_Ser641delinsTer Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Val666del Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Arg12del Uncertain significance ★★ 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/bbs12-p-cys464fs (accessed [today's date]).

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