Is DBT p.Asn326= (c.978C>T) pathogenic?

DBT p.Asn326= (c.978C>T) is classified Likely benign in DBT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.02%, amr); Associated with Inborn genetic diseases.

What condition is associated with DBT p.Asn326= (c.978C>T)?

DBT p.Asn326= (c.978C>T) is associated with Inborn genetic diseases, maple syrup urine disease (ClinVar).

How common is DBT p.Asn326= (c.978C>T) in the general population?

DBT p.Asn326= (c.978C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

DBT p.Asn326=

c.978C>T · rs140659494 · VCV736451

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Conditions

Inborn genetic diseases

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 1.9	GERP -0.52, phastCons 1
Overall
CADD	11.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,998 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00267% 43/1,613,162 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,000
Finnishnot grpmax-eligible	0.0109%	9,142
East Asian	0.00892%	11,208
Remaining individualsnot grpmax-eligible	0.0048%	20,817
African / African-American	0.00401%	24,966
South Asian	0.0022%	45,532
European (non-Finnish)	0.00102%	98,278

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: DBT
Protein: p.Asn326=
Coding: c.978C>T
MANE Select: NM_001918
dbSNP: rs140659494
Type: single nucleotide variant
Location: chr1:100210733 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 5 PDB

Full DBT 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

Also linked: maple syrup urine disease

Similar variants

DBT p.Asn326Lys Uncertain significance ★ ⚠ same residue
DBT c.1018-550A>G Pathogenic/Likely pathogenic ★★ same condition
DBT c.1281+1G>A Pathogenic/Likely pathogenic ★★ same condition
DBT c.1281+1G>T Pathogenic/Likely pathogenic ★★ same condition
DBT c.51+1G>T Pathogenic/Likely pathogenic ★★ same condition
DBT c.52-1G>A Pathogenic/Likely pathogenic ★★ same condition
DBT p.Arg291Ter Pathogenic ★★ same condition
DBT p.Arg301Cys Pathogenic/Likely pathogenic ★★ ⚠ 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/dbt-p-asn326 (accessed [today's date]).

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