Is BTD p.Asn67= (c.201C>T) pathogenic?

BTD p.Asn67= (c.201C>T) is classified Conflicting classifications of pathogenicity in BTD (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-03-01). Rare (popmax 0.561%, mid); Associated with biotinidase deficiency.

What condition is associated with BTD p.Asn67= (c.201C>T)?

BTD p.Asn67= (c.201C>T) is associated with biotinidase deficiency (ClinVar).

How common is BTD p.Asn67= (c.201C>T) in the general population?

BTD p.Asn67= (c.201C>T) is rare (popmax 0.561%, mid) (gnomAD).

How is Biotinidase deficiency inherited?

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

BTD p.Asn67=

c.201C>T · rs147057169 · VCV290069

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.561%, mid)

Conditions

biotinidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP 1.4, phastCons 0.011
Overall
CADD	8.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.561% Middle Eastern · 34/6,062 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.361%

Overall 0.203% 3,281/1,614,200 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.561%	178
Remaining individualsnot grpmax-eligible	0.248%	403
European (non-Finnish)	0.236%	424
Finnishnot grpmax-eligible	0.15%	667
Admixed American	0.148%	674
South Asian	0.0889%	1,124
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850
African / African-American	0.036%	2,780

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BTD
Protein: p.Asn67=
Coding: c.201C>T
MANE Select: NM_001370658
dbSNP: rs147057169
Type: single nucleotide variant
Location: chr3:15635640 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77
Residue 67: 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 c.1330G>C Pathogenic ★★ same condition
BTD c.249+1G>T Likely pathogenic ★★ same condition
BTD c.400-2A>G Likely pathogenic ★★ same condition
BTD c.-17+2T>C Pathogenic/Likely pathogenic ★★ same condition
BTD p.Ala142Val Pathogenic/Likely pathogenic ★★ same condition
BTD p.Ala217Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
BTD p.Ala269Val Pathogenic/Likely pathogenic ★★ same condition
BTD p.Ala279Pro Pathogenic/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-asn67 (accessed [today's date]).

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