Is BTD p.Pro371Ser (c.1111C>T) pathogenic?

BTD p.Pro371Ser (c.1111C>T) is classified Benign/Likely benign in BTD (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0712); Low-frequency (popmax 2.62%, nfe); Associated with biotinidase deficiency.

What condition is associated with BTD p.Pro371Ser (c.1111C>T)?

BTD p.Pro371Ser (c.1111C>T) is associated with biotinidase deficiency (ClinVar).

How common is BTD p.Pro371Ser (c.1111C>T) in the general population?

BTD p.Pro371Ser (c.1111C>T) is low-frequency (popmax 2.62%, nfe) (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.Pro371Ser (c.1111C>T)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

BTD p.Pro371Ser

c.1111C>T · rs35034250 · VCV38570

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.62%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

biotinidase deficiency

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -4
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.35 · regional, not allelic
Overall
CADD	6.688	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 P391S vs ClinVar P371S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.62% European (non-Finnish) · 30,956/1,180,024 alleles

Filtering AF 2.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.59%

Overall 2.13% 34,328/1,614,166 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	2.62%	38
Remaining individualsnot grpmax-eligible	1.98%	51
Finnishnot grpmax-eligible	1.13%	89
Amishnot grpmax-eligible	0.769%	130
Admixed American	0.763%	131
South Asian	0.518%	193
African / African-American	0.45%	222
Ashkenazi Jewishnot grpmax-eligible	0.436%	230
Middle Eastern	0.099%	1,010
East Asian	0.00891%	11,223

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.Pro371Ser
Coding: c.1111C>T
MANE Select: NM_001370658
dbSNP: rs35034250
Type: single nucleotide variant
Location: chr3:15645027 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77
Residue 371: a UniProt-annotated variant site (in)

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.Pro371fs 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-pro371ser (accessed [today's date]).

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