Is BBS10 p.Ser396fs (c.1187_1188del) pathogenic?

BBS10 p.Ser396fs (c.11871188del) is classified Pathogenic in BBS10 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-05-04). Very rare (popmax 0.00133%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS10 p.Ser396fs (c.1187_1188del)?

BBS10 p.Ser396fs (c.1187_1188del) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 10 (ClinVar).

How common is BBS10 p.Ser396fs (c.1187_1188del) in the general population?

BBS10 p.Ser396fs (c.1187_1188del) 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.

BBS10 p.Ser396fs

c.1187_1188del · rs1555202636 · VCV553858

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 -5.9	GERP -3.5

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 · 1/75,058 alleles

Overall 6.84e-05% 1/1,461,832 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: BBS10
Protein: p.Ser396fs
Coding: c.1187_1188del
MANE Select: NM_024685
dbSNP: rs1555202636
Type: Microsatellite
Location: chr12:76346797 (GRCh38)
Gene constraint: LOEUF 1.418 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.26

Full BBS10 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 10

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS10 p.Ser396= Likely benign ★★ same residue
BBS10 p.Ser396Ala Uncertain significance ★ ⚠ same residue
BBS10 p.Arg163fs Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Asp102fs Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Gln287fs Likely pathogenic ★★ same condition
BBS10 p.Glu104fs Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Ile190fs Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Ile504fs 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/bbs10-p-ser396fs (accessed [today's date]).

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