Is BCKDK p.Ala91Val (c.272C>T) pathogenic?

BCKDK p.Ala91Val (c.272C>T) is classified Uncertain significance in BCKDK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-09). AlphaMissense: likely pathogenic (0.67); Ultra-rare (popmax 0.0187%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BCKDK p.Ala91Val (c.272C>T)?

BCKDK p.Ala91Val (c.272C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BCKDK p.Ala91Val (c.272C>T) in the general population?

BCKDK p.Ala91Val (c.272C>T) is ultra-rare (popmax 0.0187%, nfe) (gnomAD).

What do computational predictors say about BCKDK p.Ala91Val (c.272C>T)?

AlphaMissense predicts likely pathogenic (score 0.67) — an in-silico prediction, not a clinical call.

BCKDK p.Ala91Val

c.272C>T · rs144747578 · VCV3133372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.67 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.67	likely pathogenic
REVEL	0.327	indeterminate
SaProt	LLR -13.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP -1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 3,038 bp · p 4.5e-05 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0187% European (non-Finnish) · 221/1,180,034 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0159%

Overall 0.014% 226/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0187%	5,340
Remaining individualsnot grpmax-eligible	0.0064%	15,626
African / African-American	0.00133%	75,068

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.Ala91Val
Coding: c.272C>T
MANE Select: NM_005881
dbSNP: rs144747578
Type: single nucleotide variant
Location: chr16:31109680 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.03 · 5 PDB
Residue 91: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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BCKDK p.Arg224Cys Uncertain significance ★★ ⚠ same condition
BCKDK p.Arg406Gly Uncertain significance ★★ ⚠ same condition
BCKDK p.Gln341Lys Uncertain significance ★★ ⚠ same condition
BCKDK p.Lys163Arg Uncertain significance ★★ ⚠ same condition
BCKDK p.Lys184Asn Uncertain significance ★★ ⚠ same condition
BCKDK p.Pro141Leu 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-ala91val (accessed [today's date]).

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