BBS4 p.Glu514fs
c.1541_1551del · rs748758201 · VCV813021
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (16 of 16) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP -1.6, phastCons 0.77 |
| Overall | ||
| CADD | 27.6 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0387% | 2,583 |
| African / African-American | 0.016% | 6,247 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,470 |
| South Asian | 0.00557% | 17,946 |
| European (non-Finnish) | 0.00204% | 49,067 |
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
- BBS4
- Protein
- p.Glu514fs
- Coding
- c.1541_1551del
- MANE Select
- NM_033028
- dbSNP
- rs748758201
- Type
- Deletion
- Location
- chr15:72737568 (GRCh38)
- Gene constraint
- LOEUF 0.953 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.36 · 1 PDB
- Residue 514
- the 'required for localization to centrosomes' region; the 'disordered' region
Disease context
retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Bardet-Biedl syndrome
For Retinitis pigmentosa (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
- Onset
- Adolescent, Adult, Childhood
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- BBS4 p.Glu514= Likely benign ★★ same residue
- BBS4 p.Glu514Gly Uncertain significance ★ ⚠ same residue
- BBS4 c.1064_1106+97del Pathogenic/Likely pathogenic ★★ same condition
- BBS4 p.Glu432fs Pathogenic/Likely pathogenic ★★ same condition
- BBS4 p.Leu114fs Pathogenic/Likely pathogenic ★★ same condition
- BBS4 p.Leu310fs Pathogenic/Likely pathogenic ★★ same condition
- BBS4 p.Leu381fs Pathogenic/Likely pathogenic ★★ same condition
- BBS4 p.Lys358fs 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/bbs4-p-glu514fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown