Is BTD p.Tyr433Ter (c.1298dup) pathogenic?

BTD p.Tyr433Ter (c.1298dup) is classified Likely pathogenic in BTD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-08-02). Absent from gnomAD; Associated with biotinidase deficiency.

What condition is associated with BTD p.Tyr433Ter (c.1298dup)?

BTD p.Tyr433Ter (c.1298dup) is associated with biotinidase deficiency (ClinVar).

How common is BTD p.Tyr433Ter (c.1298dup) in the general population?

BTD p.Tyr433Ter (c.1298dup) is absent from gnomAD (gnomAD).

How is Biotinidase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BTD p.Tyr433Ter

c.1298dup · rs1553654145 · VCV552997

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

biotinidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 7.8	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BTD
Protein: p.Tyr433Ter
Coding: c.1298dup
MANE Select: NM_001370658
dbSNP: rs1553654145
Type: Duplication
Location: chr3:15645213 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77

Full BTD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

biotinidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Biotinidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

BTD p.Tyr433_Tyr434insAlaLeuGlyValPheAspGlyLeuHisThrValHisGlyThrTyr Conflicting classifications of pathogenicity ★ same residue
BTD p.Tyr433Ser Uncertain significance ★ ⚠ same residue
BTD p.Cys451fs Pathogenic ★★ same condition
BTD p.Gly347fs Pathogenic/Likely pathogenic ★★ same condition
BTD p.Ile344fs Pathogenic ★★ same condition
BTD p.Leu402fs Pathogenic ★★ same condition
BTD p.Leu478fs Pathogenic ★★ same condition
BTD p.Asn307fs 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/btd-p-tyr433ter (accessed [today's date]).

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