Is DBT p.His342Asp (c.1024C>G) pathogenic?

DBT p.His342Asp (c.1024C>G) is classified Uncertain significance in DBT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-23). AlphaMissense: likely pathogenic (0.9821); Very rare (popmax 0.000257%, nfe).

How common is DBT p.His342Asp (c.1024C>G) in the general population?

DBT p.His342Asp (c.1024C>G) is very rare (popmax 0.000257%, nfe) (gnomAD).

What do computational predictors say about DBT p.His342Asp (c.1024C>G)?

AlphaMissense predicts likely pathogenic (score 0.9821) — an in-silico prediction, not a clinical call.

DBT p.His342Asp

c.1024C>G · rs398123655 · VCV93980

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9821 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9821	likely pathogenic · top 8% in DBT
REVEL	0.686	pathogenic-leaning
SaProt	LLR -15.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	31.0	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 0.000257% European (non-Finnish) · 3/1,168,252 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000207% 3/1,448,856 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.His342Asp
Coding: c.1024C>G
MANE Select: NM_001918
dbSNP: rs398123655
Type: single nucleotide variant
Location: chr1:100206630 (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

Similar variants

DBT p.His342Tyr 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
DBT p.Arg169Ter Pathogenic/Likely 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-his342asp (accessed [today's date]).

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