Is BTD p.Met378fs (c.1134delinsAA) pathogenic?

BTD p.Met378fs (c.1134delinsAA) is classified Likely pathogenic in BTD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). Associated with biotinidase deficiency.

What condition is associated with BTD p.Met378fs (c.1134delinsAA)?

BTD p.Met378fs (c.1134delinsAA) is associated with biotinidase deficiency (ClinVar).

How is Biotinidase deficiency inherited?

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

BTD p.Met378fs

c.1134delinsAA · VCV3588706

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 2.1, phastCons 1

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

Variant & gene context

Gene: BTD
Protein: p.Met378fs
Coding: c.1134delinsAA
MANE Select: NM_001370658
Type: Indel
Location: chr3:15645050 (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.Cys13fs Pathogenic ★★ same condition
BTD p.Trp389fs Pathogenic/Likely pathogenic ★★ same condition
BTD p.Cys13_Cys15delinsPheAla Pathogenic ★ same condition
BTD p.Cys159_His160delinsTer Pathogenic ★ same condition
BTD p.Phe197fs Likely pathogenic ★ same condition
BTD p.Ala251Tyr Uncertain significance ★ same condition
BTD p.Val118Phe Uncertain significance ★ same condition
BTD p.Val397Glu Uncertain significance ★ 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-met378fs (accessed [today's date]).

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