Is BTD p.Val118Phe (c.351_352delinsTT) pathogenic?

BTD p.Val118Phe (c.351352delinsTT) is classified Uncertain significance in BTD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-15). Absent from gnomAD; Associated with biotinidase deficiency.

What condition is associated with BTD p.Val118Phe (c.351_352delinsTT)?

BTD p.Val118Phe (c.351_352delinsTT) is associated with biotinidase deficiency (ClinVar).

How common is BTD p.Val118Phe (c.351_352delinsTT) in the general population?

BTD p.Val118Phe (c.351_352delinsTT) 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.Val118Phe

c.351_352delinsTT · rs2471490000 · VCV2096464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.048	GERP -4.5
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.35 · regional, not allelic

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.Val118Phe
Coding: c.351_352delinsTT
MANE Select: NM_001370658
dbSNP: rs2471490000
Type: Indel
Location: chr3:15642009 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77
Residue 118: 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.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.Met378fs Likely pathogenic ★ same condition
BTD p.Phe197fs Likely pathogenic ★ same condition
BTD p.Ala251Tyr 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-val118phe (accessed [today's date]).

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