Is DBT p.Asp127His (c.379G>C) pathogenic?

DBT p.Asp127His (c.379G>C) is classified Uncertain significance in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-17). AlphaMissense: ambiguous (0.4385); Very rare (popmax 0.00357%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DBT p.Asp127His (c.379G>C)?

DBT p.Asp127His (c.379G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DBT p.Asp127His (c.379G>C) in the general population?

DBT p.Asp127His (c.379G>C) is very rare (popmax 0.00357%, nfe) (gnomAD).

What do computational predictors say about DBT p.Asp127His (c.379G>C)?

AlphaMissense predicts ambiguous (score 0.4385) — an in-silico prediction, not a clinical call.

DBT p.Asp127His

c.379G>C · rs764683352 · VCV2230144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4385 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00357%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4385	ambiguous
REVEL	0.401	indeterminate
SaProt	LLR -13.38	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00357% European (non-Finnish) · 42/1,177,874 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.00267% 43/1,611,184 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00357%	28,045
Remaining individualsnot grpmax-eligible	0.0016%	62,378

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.Asp127His
Coding: c.379G>C
MANE Select: NM_001918
dbSNP: rs764683352
Type: single nucleotide variant
Location: chr1:100230787 (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 127: the lipoyl-binding domain; a β-strand

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

Similar variants

DBT c.1281+5A>G Uncertain significance ★★ same condition
DBT p.Arg61Cys Uncertain significance ★★ ⚠ same condition
DBT p.Cys279Phe Uncertain significance ★★ ⚠ same condition
DBT p.Thr171Ile Uncertain significance ★★ ⚠ same condition
DBT p.Thr407Ala Uncertain significance ★★ ⚠ same condition
DBT p.Asn326= Likely benign ★★ same condition
DBT p.Ala458Val Uncertain significance ★ same condition
DBT p.Arg21His Conflicting classifications of pathogenicity ★ ⚠ 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-asp127his (accessed [today's date]).

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