Is BBS12 p.Pro507fs (c.1520del) pathogenic?

BBS12 p.Pro507fs (c.1520del) is classified Likely pathogenic in BBS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-06). Very rare (popmax 0.0011%, sas); Associated with Bardet-Biedl syndrome 12.

What condition is associated with BBS12 p.Pro507fs (c.1520del)?

BBS12 p.Pro507fs (c.1520del) is associated with Bardet-Biedl syndrome 12 (ClinVar).

How common is BBS12 p.Pro507fs (c.1520del) in the general population?

BBS12 p.Pro507fs (c.1520del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS12 p.Pro507fs

c.1520del · rs2485077084 · VCV3240875

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Bardet-Biedl syndrome 12

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 3.2	GERP -3.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.84e-05% 1/1,461,894 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.Pro507fs
Coding: c.1520del
MANE Select: NM_152618
dbSNP: rs2485077084
Type: Deletion
Location: chr4:122743410 (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 12 — 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

BBS12 p.Asn485fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Asn649_Ser650insTer Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Asp383fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Asp480fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Cys304fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Gln511_Gln513del Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Glu365fs Pathogenic ★★ same condition
BBS12 p.Glu543fs 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/bbs12-p-pro507fs (accessed [today's date]).

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