BBS7 p.Arg459=
c.1377C>T · VCV4968379
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.49 | GERP -3.2, phastCons 0.99 |
| Overall | ||
| CADD | 6.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,744 alleles
Overall
6.84e-05%
1/1,461,442 alleles · very rare
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
- BBS7
- Protein
- p.Arg459=
- Coding
- c.1377C>T
- MANE Select
- NM_176824
- Type
- single nucleotide variant
- Location
- chr4:121835278 (GRCh38)
- Gene constraint
- LOEUF 0.701 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.99
Similar variants
- BBS7 p.Arg459Cys Uncertain significance ★★ ⚠ same residue
- BBS7 p.Arg459His Uncertain significance ★★ ⚠ same residue
- BBS7 p.Arg459Ser Uncertain significance ★ ⚠ same residue
- BBS7 c.1305+2T>A Likely pathogenic ★★ same type
- BBS7 c.1371+1G>A Likely pathogenic ★★ same type
- BBS7 c.1512-1G>A Likely pathogenic ★★ same type
- BBS7 c.1677-2A>G Pathogenic/Likely pathogenic ★★ same type
- BBS7 c.1891-2A>C Pathogenic/Likely pathogenic ★★ same type
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/bbs7-p-arg459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown