Is BCKDK p.Ser5= (c.15G>C) pathogenic?

BCKDK p.Ser5= (c.15G>C) is classified Likely benign in BCKDK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). Very rare (popmax 8.8e-05%, nfe); Associated with branched-chain keto acid dehydrogenase kinase deficiency.

What condition is associated with BCKDK p.Ser5= (c.15G>C)?

BCKDK p.Ser5= (c.15G>C) is associated with branched-chain keto acid dehydrogenase kinase deficiency (ClinVar).

How common is BCKDK p.Ser5= (c.15G>C) in the general population?

BCKDK p.Ser5= (c.15G>C) is very rare (popmax 8.8e-05%, nfe) (gnomAD).

BCKDK p.Ser5=

Q: How is Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency inherited?

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

c.15G>C · rs753378449 · VCV1666229

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.8e-05%, nfe)

Conditions

branched-chain keto acid dehydrogenase kinase 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 -3.4	GERP -4.5
Overall
CADD	0.906	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.8e-05% European (non-Finnish) · 1/1,136,554 alleles

Overall 6.58e-05% 1/1,519,496 alleles · very rare exomes 1/1,367,178 · genomes 0/152,318 · joint denominator

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.Ser5=
Coding: c.15G>C
MANE Select: NM_005881
dbSNP: rs753378449
Type: single nucleotide variant
Location: chr16:31109238 (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

Disease context

branched-chain keto acid dehydrogenase kinase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

BCKDK p.Arg156Ter Pathogenic ★★ same condition
BCKDK c.846-3T>A Uncertain significance ★★ same condition
BCKDK p.Ala283Thr Uncertain significance ★★ ⚠ same condition
BCKDK p.Ala29Val Uncertain significance ★★ ⚠ same condition
BCKDK p.Arg177Trp Uncertain significance ★★ ⚠ same condition
BCKDK p.Ile102Thr Uncertain significance ★★ ⚠ same condition
BCKDK p.Ile122Val Uncertain significance ★★ ⚠ same condition
BCKDK p.Ile230Met Uncertain significance ★★ ⚠ 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/bckdk-p-ser5 (accessed [today's date]).

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