Is BBS1 p.Pro245Ala (c.733C>G) pathogenic?

BBS1 p.Pro245Ala (c.733C>G) is classified Uncertain significance in BBS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-01). AlphaMissense: likely benign (0.1251); Absent from gnomAD v4.1; Associated with BBS1-related disorder.

What condition is associated with BBS1 p.Pro245Ala (c.733C>G)?

BBS1 p.Pro245Ala (c.733C>G) is associated with BBS1-related disorder (ClinVar).

How common is BBS1 p.Pro245Ala (c.733C>G) in the general population?

BBS1 p.Pro245Ala (c.733C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS1 p.Pro245Ala (c.733C>G)?

AlphaMissense predicts likely benign (score 0.1251) — an in-silico prediction, not a clinical call.

BBS1 p.Pro245Ala

c.733C>G · VCV3347539

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BBS1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1251	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -11.74	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.059 · regional, not allelic
Overall
CADD	23.1	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: BBS1
Protein: p.Pro245Ala
Coding: c.733C>G
MANE Select: NM_024649
Type: single nucleotide variant
Location: chr11:66521279 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 1 PDB
Residue 245: a UniProt-annotated variant site (in a patient with bardet-biedl syndrome)

Full BBS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BBS1-related disorder

Similar variants

BBS1 p.Pro245Leu Uncertain significance ★★ ⚠ same residue
BBS1 c.1181-9C>G Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.724-1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.952-1G>A Likely pathogenic ★★ same condition
BBS1 p.Ala447Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
BBS1 p.Arg440Ter Pathogenic/Likely pathogenic ★★ same condition
BBS1 p.Arg483Ter Pathogenic ★★ same condition
BBS1 p.Glu224Lys 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/bbs1-p-pro245ala (accessed [today's date]).

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