Is DBT p.His163fs (c.488_489del) pathogenic?

DBT p.His163fs (c.488489del) is classified Pathogenic/Likely pathogenic in DBT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-02). Very rare (popmax 0.00212%, nfe); Associated with DBT-related disorder.

What condition is associated with DBT p.His163fs (c.488_489del)?

DBT p.His163fs (c.488_489del) is associated with DBT-related disorder, maple syrup urine disease (ClinVar).

How common is DBT p.His163fs (c.488_489del) in the general population?

DBT p.His163fs (c.488_489del) is very rare (popmax 0.00212%, nfe) (gnomAD).

DBT p.His163fs

c.488_489del · rs760861011 · VCV951953

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Conditions

DBT-related disorder

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 5 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,179,902 alleles

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

Overall 0.00171% 25/1,461,742 alleles · very rare

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.His163fs
Coding: c.488_489del
MANE Select: NM_001918
dbSNP: rs760861011
Type: Microsatellite
Location: chr1:100218692 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 5 PDB
Residue 163: the 'disordered' region

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

Disease context

DBT-related disorder

Also linked: maple syrup urine disease

Similar variants

DBT p.Cys38fs Pathogenic/Likely pathogenic ★★ same condition
DBT p.Glu88del Pathogenic/Likely pathogenic ★★ same condition
DBT p.Met444_Asn445insTer Pathogenic ★★ same condition
DBT p.Thr57del Uncertain significance ★★ same condition
DBT p.Val151del Uncertain significance ★★ same condition
DBT c.*2633AAAT[7] Benign/Likely benign ★★ same condition
DBT p.Lys46fs Likely pathogenic ★ same condition
DBT p.Thr248fs 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-his163fs (accessed [today's date]).

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