Is BBS4 p.Gln60= (c.180A>G) pathogenic?

BBS4 p.Gln60= (c.180A>G) is classified Benign in BBS4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.79%, afr); Associated with Bardet-Biedl syndrome 4.

What condition is associated with BBS4 p.Gln60= (c.180A>G)?

BBS4 p.Gln60= (c.180A>G) is associated with Bardet-Biedl syndrome 4, Bardet-Biedl syndrome (ClinVar).

How common is BBS4 p.Gln60= (c.180A>G) in the general population?

BBS4 p.Gln60= (c.180A>G) is low-frequency (popmax 2.79%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS4 p.Gln60=

c.180A>G · rs114434361 · VCV434494

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.79%, afr)

Conditions

Bardet-Biedl syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.51, phastCons 1
Overall
CADD	7.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.79% African / African-American · 2,093/75,056 alleles

Filtering AF 2.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.65%

Overall 0.146% 2,352/1,614,122 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.79%	36
Remaining individualsnot grpmax-eligible	0.205%	488
Admixed American	0.168%	594
Middle Eastern	0.0495%	2,021
South Asian	0.00549%	18,211
European (non-Finnish)	0.00186%	53,635

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.Gln60=
Coding: c.180A>G
MANE Select: NM_033028
dbSNP: rs114434361
Type: single nucleotide variant
Location: chr15:72712267 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 60: the 'required for localization to centrosomes' 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

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

BBS4 p.Gln60Arg 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
BBS4 c.157-2A>G Pathogenic ★★ same condition
BBS4 c.157-3C>G 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-gln60 (accessed [today's date]).

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