Is BCKDK p.Asp216fs (c.646_649del) pathogenic?

BCKDK p.Asp216fs (c.646649del) is classified Likely pathogenic in BCKDK (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with intellectual disability.

What condition is associated with BCKDK p.Asp216fs (c.646_649del)?

BCKDK p.Asp216fs (c.646_649del) is associated with intellectual disability (ClinVar).

How common is BCKDK p.Asp216fs (c.646_649del) in the general population?

BCKDK p.Asp216fs (c.646_649del) is absent from gnomAD (gnomAD).

BCKDK p.Asp216fs

c.646_649del · rs2057404166 · VCV996751

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 0.79, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BCKDK
Protein: p.Asp216fs
Coding: c.646_649del
MANE Select: NM_005881
dbSNP: rs2057404166
Type: Deletion
Location: chr16:31110689 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.03 · 5 PDB
Residue 216: the histidine kinase domain

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCKDK c.196-14del Likely benign ★★ same type
BCKDK p.Leu17fs Pathogenic ★ same type
BCKDK p.Leu386_Gln390del Uncertain significance ★ same type
BCKDK c.196-8del Likely benign ★ same type
BCKDK c.716+19_716+20del Likely benign ★ same type
BCKDK p.Leu389fs Likely pathogenic same type
BCKDK p.Met74fs Pathogenic 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-asp216fs (accessed [today's date]).

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