Is BTD p.Leu51Pro (c.152T>C) pathogenic?

BTD p.Leu51Pro (c.152T>C) is classified Conflicting classifications of pathogenicity in BTD (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0376); Low-frequency (popmax 1.19%, sas); Associated with biotinidase deficiency.

What condition is associated with BTD p.Leu51Pro (c.152T>C)?

BTD p.Leu51Pro (c.152T>C) is associated with biotinidase deficiency (ClinVar).

How common is BTD p.Leu51Pro (c.152T>C) in the general population?

BTD p.Leu51Pro (c.152T>C) is low-frequency (popmax 1.19%, sas) (gnomAD).

How is Biotinidase deficiency inherited?

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

What do computational predictors say about BTD p.Leu51Pro (c.152T>C)?

AlphaMissense predicts likely benign (score 0.0376) — an in-silico prediction, not a clinical call.

BTD p.Leu51Pro

c.152T>C · rs397514333 · VCV38482

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0376 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.19%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

biotinidase deficiency

Computational evidence

Protein change
AlphaMissense	0.0376	likely benign
REVEL	0.428	indeterminate
SaProt	LLR -3.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -0.76
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.35 · regional, not allelic
Overall
CADD	1.301	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L71P vs ClinVar L51P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.19% South Asian · 1,081/91,084 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 0.0688% 1,110/1,614,216 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.19%	84
Remaining individualsnot grpmax-eligible	0.0384%	2,605
Middle Eastern	0.0165%	6,062
Admixed American	0.00333%	30,011
African / African-American	0.00133%	75,052
European (non-Finnish)	8.47e-05%	1,180,050

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.Leu51Pro
Coding: c.152T>C
MANE Select: NM_001370658
dbSNP: rs397514333
Type: single nucleotide variant
Location: chr3:15635591 (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 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-leu51pro (accessed [today's date]).

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