Is BTD p.Pro167fs (c.500del) pathogenic?

BTD p.Pro167fs (c.500del) is classified Pathogenic/Likely pathogenic in BTD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-04). Absent from gnomAD; Associated with biotinidase deficiency.

What condition is associated with BTD p.Pro167fs (c.500del)?

BTD p.Pro167fs (c.500del) is associated with biotinidase deficiency (ClinVar).

How common is BTD p.Pro167fs (c.500del) in the general population?

BTD p.Pro167fs (c.500del) 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.Pro167fs

c.500del · rs2125500629 · VCV1325381

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

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	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 12	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.Pro167fs
Coding: c.500del
MANE Select: NM_001370658
dbSNP: rs2125500629
Type: Deletion
Location: chr3:15644414 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77
Residue 167: the cn hydrolase domain

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.Pro167Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro167fs (accessed [today's date]).

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