Is BBS2 p.Ala504Val (c.1511C>T) pathogenic?

BBS2 p.Ala504Val (c.1511C>T) is classified Benign/Likely benign in BBS2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1008); Common (popmax 6.49%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Ala504Val (c.1511C>T)?

BBS2 p.Ala504Val (c.1511C>T) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 1, Bardet-Biedl syndrome 2 (ClinVar).

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.Ala504Val (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

BBS2 p.Ala504Val

Q: How common is BBS2 p.Ala504Val (c.1511C>T) in the general population?

BBS2 p.Ala504Val (c.1511C>T) is common (popmax 6.49%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1511C>T · rs16957538 · VCV100595

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.49%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	22.5	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 6.49% African / African-American · 4,872/75,038 alleles

Filtering AF 6.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.28%

Overall 0.365% 5,884/1,614,112 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.49%	15
Admixed American	0.506%	197
Remaining individualsnot grpmax-eligible	0.499%	200
Middle Eastern	0.363%	276
Ashkenazi Jewishnot grpmax-eligible	0.216%	463
European (non-Finnish)	0.0254%	3,933
South Asian	0.00769%	13,012
Finnishnot grpmax-eligible	0.00312%	32,009
East Asian	0.00223%	44,874

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.Ala504Val
Coding: c.1511C>T
MANE Select: NM_031885
dbSNP: rs16957538
Type: single nucleotide variant
Location: chr16:56499794 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49
Residue 504: a UniProt-annotated variant site (in)

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 1 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.Ala504= Likely benign ★ same residue
OGFOD1 p.Tyr504His 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-ala504val (accessed [today's date]).

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