Is BBS2 p.Phe460= (c.1380C>T) pathogenic?

BBS2 p.Phe460= (c.1380C>T) is classified Conflicting classifications of pathogenicity in BBS2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-03-01). Rare (popmax 0.113%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Phe460= (c.1380C>T)?

BBS2 p.Phe460= (c.1380C>T) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 2 (ClinVar).

How common is BBS2 p.Phe460= (c.1380C>T) in the general population?

BBS2 p.Phe460= (c.1380C>T) is rare (popmax 0.113%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Phe460=

c.1380C>T · rs141046144 · VCV283882

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.113%, nfe)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.71 · evaluated, not missing
Pangolin	Δ0.29	loss · gain 0.03 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -1.8	GERP -2.9
Overall
CADD	3.168	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.113% European (non-Finnish) · 1,331/1,179,988 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.0906% 1,463/1,614,056 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.113%	887
Remaining individualsnot grpmax-eligible	0.0848%	1,179
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
Finnishnot grpmax-eligible	0.0422%	2,371
Admixed American	0.02%	5,000
African / African-American	0.02%	5,001
East Asian	0.00446%	22,441
South Asian	0.0022%	45,536

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: BBS2
Protein: p.Phe460=
Coding: c.1380C>T
MANE Select: NM_031885
dbSNP: rs141046144
Type: single nucleotide variant
Location: chr16:56500871 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49

Full BBS2 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 2

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS2 c.118-1G>T Likely pathogenic ★★ same condition
BBS2 c.118-2A>C Likely pathogenic ★★ same condition
BBS2 c.118-2A>G Likely pathogenic ★★ same condition
BBS2 c.1225+2T>C Likely pathogenic ★★ same condition
BBS2 c.1225+2T>G Likely pathogenic ★★ same condition
BBS2 c.1397+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS2 c.1397+2T>C Likely pathogenic ★★ same condition
BBS2 c.1398-2A>G 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/bbs2-p-phe460 (accessed [today's date]).

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