Is DBI p.Ile28Met (c.84C>G) pathogenic?

DBI p.Ile28Met (c.84C>G) is classified Uncertain significance in DBI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.2281); Very rare (popmax 0.00754%, nfe).

How common is DBI p.Ile28Met (c.84C>G) in the general population?

DBI p.Ile28Met (c.84C>G) is very rare (popmax 0.00754%, nfe) (gnomAD).

What do computational predictors say about DBI p.Ile28Met (c.84C>G)?

AlphaMissense predicts likely benign (score 0.2281) — an in-silico prediction, not a clinical call.

DBI p.Ile28Met

c.84C>G · VCV4237707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00754%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2281	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -11.85	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	phastCons 1
Overall
CADD	20.7	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 0.00754% European (non-Finnish) · 89/1,180,018 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00595% 96/1,614,146 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00754%	13,259
Remaining individualsnot grpmax-eligible	0.0048%	20,836
Admixed American	0.00333%	30,013
Finnishnot grpmax-eligible	0.00156%	64,036
African / African-American	0.00133%	75,046

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.Ile28Met
Coding: c.84C>G
MANE Select: NM_000714 · reported on NM_001079862
Type: single nucleotide variant
Location: chr2:119368262 (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.Ile40Arg 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-ile28met (accessed [today's date]).

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