BTD p.Phe500fs
c.1499del · VCV3588708
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
biotinidase deficiency
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 (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 0.2, phastCons 0.043 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- BTD
- Protein
- p.Phe500fs
- Coding
- c.1499del
- MANE Select
- NM_001370658
- Type
- Deletion
- Location
- chr3:15645413 (GRCh38)
- Gene constraint
- LOEUF 1.22 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.77
Disease context
biotinidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Biotinidase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- BTD p.Phe500= Likely benign ★ same residue
- BTD c.250-15del Pathogenic/Likely pathogenic ★★ same condition
- BTD p.Arg144fs Pathogenic/Likely pathogenic ★★ same condition
- BTD p.Arg442fs Pathogenic/Likely pathogenic ★★ same condition
- BTD p.Arg502fs Likely pathogenic ★★ same condition
- BTD p.Cys15fs Pathogenic/Likely pathogenic ★★ same condition
- BTD p.Gln116fs Pathogenic/Likely pathogenic ★★ same condition
- BTD p.Gly14fs 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/btd-p-phe500fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown