Is BBS2 p.Val510Phe (c.1528G>T) pathogenic?

BBS2 p.Val510Phe (c.1528G>T) is classified Likely pathogenic in BBS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-10). AlphaMissense: likely benign (0.1563); Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome 1.

What condition is associated with BBS2 p.Val510Phe (c.1528G>T)?

BBS2 p.Val510Phe (c.1528G>T) is associated with Bardet-Biedl syndrome 1 (ClinVar).

How common is BBS2 p.Val510Phe (c.1528G>T) in the general population?

BBS2 p.Val510Phe (c.1528G>T) is absent from gnomAD v4.1 (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.Val510Phe (c.1528G>T)?

AlphaMissense predicts likely benign (score 0.1563) — an in-silico prediction, not a clinical call.

BBS2 p.Val510Phe

c.1528G>T · rs766098919 · VCV2502907

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1563 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome 1

Computational evidence

Protein change
AlphaMissense	0.1563	likely benign ⚠ discordant with ClinVar
REVEL	0.625	indeterminate
SaProt	LLR -10.43	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.75	acceptor loss · deltas
Pangolin	Δ0.41	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP -0.032, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	19.34	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BBS2
Protein: p.Val510Phe
Coding: c.1528G>T
MANE Select: NM_031885
dbSNP: rs766098919
Type: single nucleotide variant
Location: chr16:56498568 (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 1 — 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.Val510= Likely benign ★★ same residue
BBS2 p.Val510Ala Uncertain significance ★ ⚠ same residue
BBS2 c.1659+3A>G Benign/Likely benign ★★ same condition
BBS2 c.612+12C>A Benign ★★ same condition
BBS2 p.Ala504Val Benign/Likely benign ★★ ⚠ same condition
BBS2 c.805-20A>G Conflicting classifications of pathogenicity ★ same condition
BBS2 p.Ile123Val Conflicting classifications of pathogenicity ★ ⚠ same condition
BBS2 c.118-1G>T Likely pathogenic ★★ same type

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-val510phe (accessed [today's date]).

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