Is BBS4 p.Ser138fs (c.412del) pathogenic?

BBS4 p.Ser138fs (c.412del) is classified Likely pathogenic in BBS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). Very rare (popmax 6.84e-05%); Associated with Bardet-Biedl syndrome 4.

What condition is associated with BBS4 p.Ser138fs (c.412del)?

BBS4 p.Ser138fs (c.412del) is associated with Bardet-Biedl syndrome 4 (ClinVar).

How common is BBS4 p.Ser138fs (c.412del) in the general population?

BBS4 p.Ser138fs (c.412del) is very rare (popmax 6.84e-05%) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS4 p.Ser138fs

c.412del · rs2542969256 · VCV3240897

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 6.84e-05%)

Conditions

Bardet-Biedl syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -0.55, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,472 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: BBS4
Protein: p.Ser138fs
Coding: c.412del
MANE Select: NM_033028
dbSNP: rs2542969256
Type: Deletion
Location: chr15:72722800 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 138: the 'interaction with pcm1' region

Full BBS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 4 — 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

BBS4 p.Ser138_Val143del Uncertain significance ★ same residue
BBS4 c.1064_1106+97del Pathogenic/Likely pathogenic ★★ same condition
BBS4 p.Ala467fs Likely pathogenic ★★ same condition
BBS4 p.Leu114fs Pathogenic/Likely pathogenic ★★ same condition
BBS4 p.Leu310fs Pathogenic/Likely pathogenic ★★ same condition
BBS4 p.Leu381fs Pathogenic/Likely pathogenic ★★ same condition
BBS4 p.Lys358fs Pathogenic/Likely pathogenic ★★ same condition
BBS4 p.Pro30fs 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/bbs4-p-ser138fs (accessed [today's date]).

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