Is BBS1 p.Ala264Pro (c.790G>C) pathogenic?

BBS1 p.Ala264Pro (c.790G>C) is classified Uncertain significance in BBS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely pathogenic (0.5786); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS1 p.Ala264Pro (c.790G>C)?

BBS1 p.Ala264Pro (c.790G>C) is associated with Inborn genetic diseases (ClinVar).

How common is BBS1 p.Ala264Pro (c.790G>C) in the general population?

BBS1 p.Ala264Pro (c.790G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS1 p.Ala264Pro (c.790G>C)?

AlphaMissense predicts likely pathogenic (score 0.5786) — an in-silico prediction, not a clinical call.

BBS1 p.Ala264Pro

c.790G>C · rs1483861573 · VCV3133148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5786 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5786	likely pathogenic
REVEL	0.385	indeterminate
SaProt	LLR -13.70	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.059 · regional, not allelic
Overall
CADD	19.21	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: BBS1
Protein: p.Ala264Pro
Coding: c.790G>C
MANE Select: NM_024649
dbSNP: rs1483861573
Type: single nucleotide variant
Location: chr11:66521336 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 1 PDB

Full BBS1 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

BBS1 p.Ala264= Likely benign ★★ same residue
BBS1 p.Ala142Ser Uncertain significance ★★ ⚠ same condition
BBS1 p.Ala184Val Uncertain significance ★★ ⚠ same condition
BBS1 p.Ala580Thr Uncertain significance ★★ ⚠ same condition
BBS1 p.Arg393Gln Uncertain significance ★★ ⚠ same condition
BBS1 p.Arg429Gln Uncertain significance ★★ ⚠ same condition
BBS1 p.Gln170Arg Uncertain significance ★★ ⚠ same condition
BBS1 p.Gln64His 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/bbs1-p-ala264pro (accessed [today's date]).

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