Is BBS2 p.Ala564Val (c.1691C>T) pathogenic?

BBS2 p.Ala564Val (c.1691C>T) is classified Uncertain significance in BBS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.3336); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS2 p.Ala564Val (c.1691C>T)?

BBS2 p.Ala564Val (c.1691C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BBS2 p.Ala564Val (c.1691C>T) in the general population?

BBS2 p.Ala564Val (c.1691C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS2 p.Ala564Val (c.1691C>T)?

AlphaMissense predicts likely benign (score 0.3336) — an in-silico prediction, not a clinical call.

BBS2 p.Ala564Val

c.1691C>T · VCV4595006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3336 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3336	likely benign
REVEL	0.747	pathogenic-leaning
SaProt	LLR -7.87	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	27.7	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.Ala564Val
Coding: c.1691C>T
MANE Select: NM_031885
Type: single nucleotide variant
Location: chr16:56497849 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BBS2 p.Ala564Ser Uncertain significance ★ ⚠ same residue
BBS2 p.Ala564Thr Uncertain significance ★ ⚠ same residue
BBS2 p.Ala682Thr Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg353Cys Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg374Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg539Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg622Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg661His Uncertain significance ★★ ⚠ 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-ala564val (accessed [today's date]).

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