Is DBT p.Gln378Pro (c.1133A>C) pathogenic?

DBT p.Gln378Pro (c.1133A>C) is classified Uncertain significance in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2013-09-04). AlphaMissense: likely pathogenic (0.8808); Absent from gnomAD v4.1.

How common is DBT p.Gln378Pro (c.1133A>C) in the general population?

DBT p.Gln378Pro (c.1133A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DBT p.Gln378Pro (c.1133A>C)?

AlphaMissense predicts likely pathogenic (score 0.8808) — an in-silico prediction, not a clinical call.

DBT p.Gln378Pro

c.1133A>C · rs398123657 · VCV93983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8808 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8808	likely pathogenic
REVEL	0.471	indeterminate
SaProt	LLR -14.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DBT
Protein: p.Gln378Pro
Coding: c.1133A>C
MANE Select: NM_001918
dbSNP: rs398123657
Type: single nucleotide variant
Location: chr1:100206521 (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 378: a binding site

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

Similar variants

DBT p.Gln378Ter Pathogenic ★ same residue
DBT p.Gln378Arg Uncertain significance ★ ⚠ same residue
DBT c.1018-550A>G Pathogenic/Likely pathogenic ★★ same type
DBT c.1281+1G>A Pathogenic/Likely pathogenic ★★ same type
DBT c.1281+1G>T Pathogenic/Likely pathogenic ★★ same type
DBT c.51+1G>T Pathogenic/Likely pathogenic ★★ same type
DBT c.52-1G>A Pathogenic/Likely pathogenic ★★ same type
DBT c.773-2A>G 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/dbt-p-gln378pro (accessed [today's date]).

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