Is DBI p.Arg44Trp (c.130C>T) pathogenic?

DBI p.Arg44Trp (c.130C>T) is classified Uncertain significance in DBI (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-27). AlphaMissense: ambiguous (0.461); Ultra-rare (popmax 0.0352%, sas).

How common is DBI p.Arg44Trp (c.130C>T) in the general population?

DBI p.Arg44Trp (c.130C>T) is ultra-rare (popmax 0.0352%, sas) (gnomAD).

What do computational predictors say about DBI p.Arg44Trp (c.130C>T)?

AlphaMissense predicts ambiguous (score 0.461) — an in-silico prediction, not a clinical call.

DBI p.Arg44Trp

c.130C>T · rs144004233 · VCV2400033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.461 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0352%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.461	ambiguous
REVEL	0.27	benign-leaning
SaProt	LLR -14.22	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	phastCons 1
Overall
CADD	25.1	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 0.0352% South Asian · 32/91,008 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0223%

Overall 0.00855% 138/1,613,726 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0352%	2,844
Admixed American	0.0283%	3,528
Remaining individualsnot grpmax-eligible	0.008%	12,498
European (non-Finnish)	0.00687%	14,565
African / African-American	0.00267%	37,504
East Asian	0.00223%	44,878

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.Arg44Trp
Coding: c.130C>T
MANE Select: NM_000714 · reported on NM_001079862
dbSNP: rs144004233
Type: single nucleotide variant
Location: chr2:119370742 (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.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.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-arg44trp (accessed [today's date]).

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