Is BCKDK p.Ile320= (c.960C>T) pathogenic?

BCKDK p.Ile320= (c.960C>T) is classified Likely benign in BCKDK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-28). Very rare (popmax 0.00223%, eas); Associated with branched-chain keto acid dehydrogenase kinase deficiency.

What condition is associated with BCKDK p.Ile320= (c.960C>T)?

BCKDK p.Ile320= (c.960C>T) is associated with branched-chain keto acid dehydrogenase kinase deficiency (ClinVar).

How common is BCKDK p.Ile320= (c.960C>T) in the general population?

BCKDK p.Ile320= (c.960C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

BCKDK p.Ile320=

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.960C>T · rs999998050 · VCV2646469

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -5.5	GERP -4.4
Overall
CADD	2.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,896 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00198% 32/1,613,986 alleles · very rare exomes 29/1,461,850 · genomes 3/152,136 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,241
East Asiangrpmax	0.00223%	44,896
South Asian	0.0022%	45,542
European (non-Finnish)	0.00212%	47,201
Admixed American	0.00167%	59,992
African / African-American	0.00133%	74,908

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile320=
Coding: c.960C>T
MANE Select: NM_005881
dbSNP: rs999998050
Type: single nucleotide variant
Location: chr16:31111893 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.03 · 5 PDB
Residue 320: the histidine kinase domain

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-ile320 (accessed [today's date]).

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