Is BBS12 p.Ser384fs (c.1151del) pathogenic?

BBS12 p.Ser384fs (c.1151del) is classified Pathogenic/Likely pathogenic in BBS12 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-04). Very rare (popmax 0.00267%, afr); Associated with BBS12-related disorder.

What condition is associated with BBS12 p.Ser384fs (c.1151del)?

BBS12 p.Ser384fs (c.1151del) is associated with BBS12-related disorder, Bardet-Biedl syndrome 12, Bardet-Biedl syndrome (ClinVar).

How common is BBS12 p.Ser384fs (c.1151del) in the general population?

BBS12 p.Ser384fs (c.1151del) is very rare (popmax 0.00267%, afr) (gnomAD).

BBS12 p.Ser384fs

c.1151del · rs1553941404 · VCV550386

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

BBS12-related disorder

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 0.52	GERP -0.5
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,958 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,614,152 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,479
Admixed American	0.00167%	60,014
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ser384fs
Coding: c.1151del
MANE Select: NM_152618
dbSNP: rs1553941404
Type: Deletion
Location: chr4:122743043 (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

BBS12-related disorder

Also linked: Bardet-Biedl syndrome 12 Bardet-Biedl syndrome

Similar variants

BBS12 p.Ser384= Likely benign ★ same residue
BBS12 p.Ser384Thr Uncertain significance ⚠ 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

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-ser384fs (accessed [today's date]).

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