Is BBS1 p.Arg341Pro (c.1022G>C) pathogenic?

BBS1 p.Arg341Pro (c.1022G>C) is classified Uncertain significance in BBS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: ambiguous (0.516); Very rare (popmax 0.000339%, nfe); Associated with Bardet-Biedl syndrome 1.

What condition is associated with BBS1 p.Arg341Pro (c.1022G>C)?

BBS1 p.Arg341Pro (c.1022G>C) is associated with Bardet-Biedl syndrome 1 (ClinVar).

How common is BBS1 p.Arg341Pro (c.1022G>C) in the general population?

BBS1 p.Arg341Pro (c.1022G>C) is very rare (popmax 0.000339%, nfe) (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 BBS1 p.Arg341Pro (c.1022G>C)?

AlphaMissense predicts ambiguous (score 0.516) — an in-silico prediction, not a clinical call.

BBS1 p.Arg341Pro

c.1022G>C · VCV3600119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Bardet-Biedl syndrome 1

Computational evidence

Protein change
AlphaMissense	0.516	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -9.80	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.059 · regional, not allelic
Overall
CADD	27.1	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,006 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,408 alleles · very rare exomes 4/1,461,108 · genomes 0/152,300 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BBS1
Protein: p.Arg341Pro
Coding: c.1022G>C
MANE Select: NM_024649
Type: single nucleotide variant
Location: chr11:66523794 (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

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

BBS1 p.Arg341Gln Uncertain significance ★★ ⚠ same residue
BBS1 c.1110+3G>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.1111-2A>G Likely pathogenic ★★ same condition
BBS1 c.1181-9C>G Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.124+1G>A Pathogenic ★★ same condition
BBS1 c.124+1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.1608+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS1 c.432+1G>A 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-arg341pro (accessed [today's date]).

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