Is BTD p.Arg144= (c.430A>C) pathogenic?

BTD p.Arg144= (c.430A>C) is classified Likely benign in BTD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Rare (popmax 0.199%, sas); Associated with biotinidase deficiency.

What condition is associated with BTD p.Arg144= (c.430A>C)?

BTD p.Arg144= (c.430A>C) is associated with biotinidase deficiency (ClinVar).

How common is BTD p.Arg144= (c.430A>C) in the general population?

BTD p.Arg144= (c.430A>C) is rare (popmax 0.199%, sas) (gnomAD).

How is Biotinidase deficiency inherited?

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

BTD p.Arg144=

c.430A>C · rs556096072 · VCV1148541

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.199%, sas)

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 5.2	GERP 0.066, phastCons 0.46
Overall
CADD	9.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.199% South Asian · 181/91,032 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.166%

Overall 0.012% 194/1,613,828 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.199%	503
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,417
European (non-Finnish)	0.000509%	196,655

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.Arg144=
Coding: c.430A>C
MANE Select: NM_001370658
dbSNP: rs556096072
Type: single nucleotide variant
Location: chr3:15644346 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77
Residue 144: 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.Arg144fs Pathogenic/Likely pathogenic ★★ same residue
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

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-arg144 (accessed [today's date]).

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