Is DBT p.Leu398Phe (c.1192C>T) pathogenic?

DBT p.Leu398Phe (c.1192C>T) is classified Uncertain significance in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: ambiguous (0.3892); Absent from gnomAD v4.1.

How common is DBT p.Leu398Phe (c.1192C>T) in the general population?

DBT p.Leu398Phe (c.1192C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DBT p.Leu398Phe (c.1192C>T)?

AlphaMissense predicts ambiguous (score 0.3892) — an in-silico prediction, not a clinical call.

DBT p.Leu398Phe

c.1192C>T · VCV3335994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3892 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3892	ambiguous
REVEL	0.34	indeterminate
SaProt	LLR -10.96	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.93, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	24.0	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

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.Leu398Phe
Coding: c.1192C>T
MANE Select: NM_001918
Type: single nucleotide variant
Location: chr1:100206462 (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 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
DBT p.Arg291Ter 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-leu398phe (accessed [today's date]).

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