Is DBI p.Ile40Arg (c.119T>G) pathogenic?

DBI p.Ile40Arg (c.119T>G) is classified Uncertain significance in DBI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely pathogenic (0.7019); Ultra-rare (popmax 0.0387%, afr).

How common is DBI p.Ile40Arg (c.119T>G) in the general population?

DBI p.Ile40Arg (c.119T>G) is ultra-rare (popmax 0.0387%, afr) (gnomAD).

What do computational predictors say about DBI p.Ile40Arg (c.119T>G)?

AlphaMissense predicts likely pathogenic (score 0.7019) — an in-silico prediction, not a clinical call.

DBI p.Ile40Arg

c.119T>G · VCV3499765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7019 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0387%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7019	likely pathogenic
REVEL	0.329	indeterminate
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	phastCons 1
Overall
CADD	23.8	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 0.0387% African / African-American · 29/74,854 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.00192% 31/1,611,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0387%	2,581
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,410

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: DBI
Protein: p.Ile40Arg
Coding: c.119T>G
MANE Select: NM_000714 · reported on NM_001079862
Type: single nucleotide variant
Location: chr2:119368297 (GRCh38)
Structure: AlphaFold pLDDT 44.67

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

Similar variants

DBI p.Ala35Val Uncertain significance ★ ⚠ same type
DBI p.Arg14Ser Uncertain significance ★ ⚠ same type
DBI p.Arg44Trp Uncertain significance ★ ⚠ same type
DBI p.Asp57Gly Uncertain significance ★ ⚠ same type
DBI p.Glu24Gln Uncertain significance ★ ⚠ same type
DBI p.Gly64Ala Uncertain significance ★ ⚠ same type
DBI p.Ile28Met Uncertain significance ★ ⚠ same type
DBI p.Lys67Arg Uncertain significance ★ ⚠ 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/dbi-p-ile40arg (accessed [today's date]).

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