Is DBT p.Ile72Val (c.214A>G) pathogenic?

DBT p.Ile72Val (c.214A>G) is classified Uncertain significance in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: ambiguous (0.4052); Very rare (popmax 0.00224%, eas).

How common is DBT p.Ile72Val (c.214A>G) in the general population?

DBT p.Ile72Val (c.214A>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about DBT p.Ile72Val (c.214A>G)?

AlphaMissense predicts ambiguous (score 0.4052) — an in-silico prediction, not a clinical call.

DBT p.Ile72Val

c.214A>G · VCV3771534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Computational evidence

Protein change
AlphaMissense	0.4052	ambiguous
REVEL	0.355	indeterminate
SaProt	LLR -10.78	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	23.9	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 0.00224% East Asian · 1/44,616 alleles

Overall 0.000138% 2/1,444,748 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,616
South Asian	0.00111%	90,018

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.Ile72Val
Coding: c.214A>G
MANE Select: NM_001918
Type: single nucleotide variant
Location: chr1:100235473 (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 72: the lipoyl-binding domain

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

Similar variants

DBT p.Ile72Thr 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-ile72val (accessed [today's date]).

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