Is BBS10 p.Ala596Val (c.1787C>T) pathogenic?

BBS10 p.Ala596Val (c.1787C>T) is classified Uncertain significance in BBS10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-24). AlphaMissense: likely benign (0.2009); Absent from gnomAD v4.1; Associated with BBS10-related disorder.

What condition is associated with BBS10 p.Ala596Val (c.1787C>T)?

BBS10 p.Ala596Val (c.1787C>T) is associated with BBS10-related disorder (ClinVar).

How common is BBS10 p.Ala596Val (c.1787C>T) in the general population?

BBS10 p.Ala596Val (c.1787C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS10 p.Ala596Val (c.1787C>T)?

AlphaMissense predicts likely benign (score 0.2009) — an in-silico prediction, not a clinical call.

BBS10 p.Ala596Val

c.1787C>T · VCV3348200

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2009 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

BBS10-related disorder

Computational evidence

Protein change
AlphaMissense	0.2009	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP -0.008, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,542 bp · p 1 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: BBS10
Protein: p.Ala596Val
Coding: c.1787C>T
MANE Select: NM_024685
Type: single nucleotide variant
Location: chr12:76346198 (GRCh38)
Gene constraint: LOEUF 1.418 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.26
Residue 596: a UniProt-annotated variant site (in bbs10; uncertain significance)

Full BBS10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BBS10-related disorder

Similar variants

BBS10 p.Ala596= Likely benign ★ same residue
BBS10 p.Arg49Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
BBS10 p.Cys91Trp Pathogenic ★★ ⚠ same condition
BBS10 p.Gln137Ter Pathogenic ★★ same condition
BBS10 p.Gln192Ter Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Gln284Ter Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Glu499Ter Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.His395Arg 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/bbs10-p-ala596val (accessed [today's date]).

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