Is BTD p.Cys13fs (c.38_44delinsTCC) pathogenic?

BTD p.Cys13fs (c.3844delinsTCC) is classified Pathogenic in BTD (ClinVar, Multiple submitters, 26 submitters; last evaluated 2026-01-26). Absent from gnomAD; Associated with BTD-related disorder.

What condition is associated with BTD p.Cys13fs (c.38_44delinsTCC)?

BTD p.Cys13fs (c.38_44delinsTCC) is associated with BTD-related disorder, biotinidase deficiency (ClinVar).

How common is BTD p.Cys13fs (c.38_44delinsTCC) in the general population?

BTD p.Cys13fs (c.38_44delinsTCC) is absent from gnomAD (gnomAD).

BTD p.Cys13fs

c.38_44delinsTCC · rs80338684 · VCV1895

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 26 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

BTD-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP 0.3, phastCons 0.42

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.Cys13fs
Coding: c.38_44delinsTCC
MANE Select: NM_001370658
dbSNP: rs80338684
Type: Indel
Location: chr3:15635477 (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

BTD-related disorder

Also linked: biotinidase deficiency

Similar variants

BTD p.Cys13_Cys15delinsPheAla Pathogenic ★ same residue
BTD p.Cys13= Likely benign ★★ same residue
BTD p.Cys13Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
BTD p.Trp389fs Pathogenic/Likely 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

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-cys13fs (accessed [today's date]).

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