Is BBS12 p.Val381fs (c.1140_1141del) pathogenic?

BBS12 p.Val381fs (c.11401141del) is classified Pathogenic/Likely pathogenic in BBS12 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-10). Very rare (popmax 0.00133%, afr); Associated with Bardet-Biedl syndrome 12.

What condition is associated with BBS12 p.Val381fs (c.1140_1141del)?

BBS12 p.Val381fs (c.1140_1141del) is associated with Bardet-Biedl syndrome 12, Bardet-Biedl syndrome (ClinVar).

How common is BBS12 p.Val381fs (c.1140_1141del) in the general population?

BBS12 p.Val381fs (c.1140_1141del) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS12 p.Val381fs

c.1140_1141del · rs1553941391 · VCV550298

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 -0.13	GERP 1.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,048 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-Americangrpmax	0.00133%	75,048
European (non-Finnish)	0.000254%	393,345

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val381fs
Coding: c.1140_1141del
MANE Select: NM_152618
dbSNP: rs1553941391
Type: Deletion
Location: chr4:122743032 (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

Also linked: Bardet-Biedl syndrome

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.Val381= Likely benign ★ same residue
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.Cys140fs Pathogenic ★★ same condition
BBS12 p.Cys304fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Gln511_Gln513del 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-val381fs (accessed [today's date]).

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