Is BBS4 p.Glu4Ter (c.10G>T) pathogenic?

BBS4 p.Glu4Ter (c.10G>T) is classified Pathogenic/Likely pathogenic in BBS4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-04). Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome.

What condition is associated with BBS4 p.Glu4Ter (c.10G>T)?

BBS4 p.Glu4Ter (c.10G>T) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 4 (ClinVar).

How common is BBS4 p.Glu4Ter (c.10G>T) in the general population?

BBS4 p.Glu4Ter (c.10G>T) is absent from gnomAD v4.1 (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS4 p.Glu4Ter

c.10G>T · rs1336636537 · VCV2197130

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,566,070)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.4, phastCons 1
Overall
CADD	49.0	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

No allele count reported in gnomAD v4.1 (AN 1,566,070). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BBS4
Protein: p.Glu4Ter
Coding: c.10G>T
MANE Select: NM_033028
dbSNP: rs1336636537
Type: single nucleotide variant
Location: chr15:72686237 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 4: the 'required for localization to centrosomes' region; the 'disordered' region

Full BBS4 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 4

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.Glu4= Likely benign ★★ same residue
BBS4 p.Glu4Gln Uncertain significance ★ ⚠ same residue
BBS4 p.Glu4Lys Uncertain significance ★ ⚠ same residue
BBS4 c.1106+2T>A Pathogenic/Likely pathogenic ★★ same condition
BBS4 c.1248+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS4 c.1248+1G>T Pathogenic ★★ same condition
BBS4 c.1248+2T>C Pathogenic/Likely pathogenic ★★ same condition
BBS4 c.1249-2A>C 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-glu4ter (accessed [today's date]).

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