Is BCKDK p.Thr205= (c.615G>A) pathogenic?

BCKDK p.Thr205= (c.615G>A) is classified Benign in BCKDK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 90.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with branched-chain keto acid dehydrogenase kinase deficiency.

What condition is associated with BCKDK p.Thr205= (c.615G>A)?

BCKDK p.Thr205= (c.615G>A) is associated with branched-chain keto acid dehydrogenase kinase deficiency (ClinVar).

BCKDK p.Thr205=

Q: How common is BCKDK p.Thr205= (c.615G>A) in the general population?

BCKDK p.Thr205= (c.615G>A) is common (popmax 90.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.615G>A · rs14235 · VCV128521

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 90.2%, eas) — too common for a highly-penetrant pathogenic allele

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 -4	GERP -4.1
Overall
CADD	2.869	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.2% East Asian · 40,474/44,864 alleles

Filtering AF 89.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.2%

Overall 36.4% 587,284/1,613,534 alleles · common exomes 539,126/1,461,504 · genomes 48,158/152,030 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	90.2%	1
Middle Eastern	49.1%	2
Ashkenazi Jewishnot grpmax-eligible	48.7%	2
Amishnot grpmax-eligible	43.3%	2
Admixed American	43%	2
Finnishnot grpmax-eligible	38.9%	3
Remaining individualsnot grpmax-eligible	38.4%	3
European (non-Finnish)	36.4%	3
South Asian	18%	6
African / African-American	12%	8

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.Thr205=
Coding: c.615G>A
MANE Select: NM_005881
dbSNP: rs14235
Type: single nucleotide variant
Location: chr16:31110472 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.03 · 5 PDB
Residue 205: the histidine kinase domain; an α-helix

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-thr205 (accessed [today's date]).

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