Is BCKDK p.Pro16Leu (c.47C>T) pathogenic?

BCKDK p.Pro16Leu (c.47C>T) is classified Uncertain significance in BCKDK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-10). AlphaMissense: likely benign (0.0992); Very rare (popmax 0.00345%, sas).

How common is BCKDK p.Pro16Leu (c.47C>T) in the general population?

BCKDK p.Pro16Leu (c.47C>T) is very rare (popmax 0.00345%, sas) (gnomAD).

What do computational predictors say about BCKDK p.Pro16Leu (c.47C>T)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

BCKDK p.Pro16Leu

c.47C>T · rs749467687 · VCV195254

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00345%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.50	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 1	GERP -1.1, phastCons 0.001
Regional constraint	o/e 0.83	unconstrained · MANE · 3,038 bp · p 4.5e-05 · regional, not allelic
Overall
CADD	15.87	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00345% South Asian · 3/86,908 alleles

Filtering AF 0.000917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000454%

Overall 0.000892% 14/1,569,648 alleles · very rare exomes 12/1,417,480 · genomes 2/152,168 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00345%	28,969
European (non-Finnish)	0.000949%	105,347

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: BCKDK
Protein: p.Pro16Leu
Coding: c.47C>T
MANE Select: NM_005881
dbSNP: rs749467687
Type: single nucleotide variant
Location: chr16:31109270 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.03 · 5 PDB

Full BCKDK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCKDK p.Arg156Ter Pathogenic ★★ same type
BCKDK c.846-3T>A Uncertain significance ★★ same type
BCKDK p.Ala283Thr Uncertain significance ★★ ⚠ same type
BCKDK p.Ala29Val Uncertain significance ★★ ⚠ same type
BCKDK p.Arg177Trp Uncertain significance ★★ ⚠ same type
BCKDK p.Arg224Cys Uncertain significance ★★ ⚠ same type
BCKDK p.Arg406Gly Uncertain significance ★★ ⚠ same type
BCKDK p.Gln341Lys Uncertain significance ★★ ⚠ same type

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/bckdk-p-pro16leu (accessed [today's date]).

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