Is BBS2 p.Ala564Ser (c.1690G>T) pathogenic?

BBS2 p.Ala564Ser (c.1690G>T) is classified Uncertain significance in BBS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: likely benign (0.2524); Ultra-rare (popmax 0.0516%, sas); Associated with Bardet-Biedl syndrome 2.

What condition is associated with BBS2 p.Ala564Ser (c.1690G>T)?

BBS2 p.Ala564Ser (c.1690G>T) is associated with Bardet-Biedl syndrome 2 (ClinVar).

How common is BBS2 p.Ala564Ser (c.1690G>T) in the general population?

BBS2 p.Ala564Ser (c.1690G>T) is ultra-rare (popmax 0.0516%, sas) (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.Ala564Ser (c.1690G>T)?

AlphaMissense predicts likely benign (score 0.2524) — an in-silico prediction, not a clinical call.

BBS2 p.Ala564Ser

c.1690G>T · rs780747680 · VCV2500754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2524 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0516%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome 2

Computational evidence

Protein change
AlphaMissense	0.2524	likely benign
REVEL	0.875	moderately pathogenic-leaning
SaProt	LLR -7.70	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	26.9	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 0.0516% South Asian · 47/91,056 alleles

Filtering AF 0.0399% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.00336% 49/1,459,906 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0516%	1,937
European (non-Finnish)	0.00017%	589,883

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.Ala564Ser
Coding: c.1690G>T
MANE Select: NM_031885
dbSNP: rs780747680
Type: single nucleotide variant
Location: chr16:56497850 (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 2 — 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.Ala564Thr Uncertain significance ★ ⚠ same residue
BBS2 p.Ala564Val Uncertain significance ★ ⚠ 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-ala564ser (accessed [today's date]).

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