Is DBT p.Leu284Phe (c.850C>T) pathogenic?

DBT p.Leu284Phe (c.850C>T) is classified Uncertain significance in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: ambiguous (0.4376); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with DBT p.Leu284Phe (c.850C>T)?

DBT p.Leu284Phe (c.850C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DBT p.Leu284Phe (c.850C>T) in the general population?

DBT p.Leu284Phe (c.850C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DBT p.Leu284Phe (c.850C>T)?

AlphaMissense predicts ambiguous (score 0.4376) — an in-silico prediction, not a clinical call.

DBT p.Leu284Phe

c.850C>T · VCV4237760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4376 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4376	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -8.51	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP -2.6, phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	19.14	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 0.0011% South Asian · 1/91,070 alleles

Overall 6.84e-05% 1/1,461,284 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.Leu284Phe
Coding: c.850C>T
MANE Select: NM_001918
Type: single nucleotide variant
Location: chr1:100214906 (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

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-leu284phe (accessed [today's date]).

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