Is BBS2 p.Leu514= (c.1542C>T) pathogenic?

BBS2 p.Leu514= (c.1542C>T) is classified Likely benign in BBS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). Very rare (popmax 0.00401%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Leu514= (c.1542C>T)?

BBS2 p.Leu514= (c.1542C>T) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Leu514= (c.1542C>T) in the general population?

BBS2 p.Leu514= (c.1542C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Leu514=

c.1542C>T · rs374156464 · VCV1126312

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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>T here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.2	GERP -0.93, phastCons 1
Overall
CADD	5.304	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,816 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000744% 12/1,613,718 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,939
South Asian	0.00329%	30,359
East Asian	0.00223%	44,862
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	63,926
European (non-Finnish)	0.000254%	393,324

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.Leu514=
Coding: c.1542C>T
MANE Select: NM_031885
dbSNP: rs374156464
Type: single nucleotide variant
Location: chr16:56498554 (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

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS2 p.Leu514Phe Uncertain significance ★ ⚠ same residue
BBS2 c.118-1G>T Likely pathogenic ★★ same condition
BBS2 c.118-2A>C Likely pathogenic ★★ same condition
BBS2 c.1225+2T>C 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
BBS2 c.1527+1G>A 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-leu514 (accessed [today's date]).

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