Is BBS2 p.Val510= (c.1530T>G) pathogenic?

BBS2 p.Val510= (c.1530T>G) is classified Likely benign in BBS2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-20). Very rare (popmax 0.00446%, eas); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Val510= (c.1530T>G)?

BBS2 p.Val510= (c.1530T>G) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Val510= (c.1530T>G) in the general population?

BBS2 p.Val510= (c.1530T>G) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Val510=

c.1530T>G · rs545597883 · VCV1116418

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 · A>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.054	GERP -3.8
Overall
CADD	0.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,856 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000929% 15/1,614,080 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,835
East Asiangrpmax	0.00446%	22,428
African / African-American	0.004%	25,013
Admixed American	0.00167%	60,030
European (non-Finnish)	0.000508%	196,667

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val510=
Coding: c.1530T>G
MANE Select: NM_031885
dbSNP: rs545597883
Type: single nucleotide variant
Location: chr16:56498566 (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 retinitis pigmentosa 74

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.Val510Ala Uncertain significance ★ ⚠ same residue
BBS2 p.Val510Phe Likely pathogenic ⚠ same residue
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

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-val510 (accessed [today's date]).

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