Is BBS2 p.Gln508Pro (c.1523A>C) pathogenic?

BBS2 p.Gln508Pro (c.1523A>C) is classified Conflicting classifications of pathogenicity in BBS2 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0905); Rare (popmax 0.212%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Gln508Pro (c.1523A>C)?

BBS2 p.Gln508Pro (c.1523A>C) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 2 (ClinVar).

How common is BBS2 p.Gln508Pro (c.1523A>C) in the general population?

BBS2 p.Gln508Pro (c.1523A>C) is rare (popmax 0.212%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

What do computational predictors say about BBS2 p.Gln508Pro (c.1523A>C)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

BBS2 p.Gln508Pro

c.1523A>C · rs115328064 · VCV216780

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.212%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.756	pathogenic-leaning
SaProt	LLR -7.41	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.51, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.212% African / African-American · 159/75,072 alleles

Filtering AF 0.185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.0154% 248/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.212%	472
Middle Eastern	0.132%	758
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Admixed American	0.0233%	4,288
European (non-Finnish)	0.00424%	23,600

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.Gln508Pro
Coding: c.1523A>C
MANE Select: NM_031885
dbSNP: rs115328064
Type: single nucleotide variant
Location: chr16:56499782 (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 p.Gln508= Likely benign ★ 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
BBS2 c.1397+2T>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/bbs2-p-gln508pro (accessed [today's date]).

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