Is DBX2 p.Arg184Trp (c.550C>T) pathogenic?

DBX2 p.Arg184Trp (c.550C>T) is classified Uncertain significance in DBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2669); Ultra-rare (popmax 0.0417%, afr).

How common is DBX2 p.Arg184Trp (c.550C>T) in the general population?

DBX2 p.Arg184Trp (c.550C>T) is ultra-rare (popmax 0.0417%, afr) (gnomAD).

What do computational predictors say about DBX2 p.Arg184Trp (c.550C>T)?

AlphaMissense predicts likely benign (score 0.2669) — an in-silico prediction, not a clinical call.

DBX2 p.Arg184Trp

c.550C>T · VCV4237773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2669 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2669	likely benign
REVEL	0.672	pathogenic-leaning
SaProt	LLR -14.83	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 35 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	26.4	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 0.0417% African / African-American · 31/74,422 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.00337% 54/1,603,366 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0417%	2,401
Admixed American	0.00684%	14,617
Remaining individualsnot grpmax-eligible	0.00645%	15,513
South Asian	0.00563%	17,764
East Asian	0.00447%	22,384
European (non-Finnish)	0.000681%	146,949

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: DBX2
Protein: p.Arg184Trp
Coding: c.550C>T
MANE Select: NM_001004329
Type: single nucleotide variant
Location: chr12:45023844 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.74

Full DBX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBX2 p.Arg267= Benign ★★ same type
DBX2 p.Ala104Val Uncertain significance ★ ⚠ same type
DBX2 p.Ala10Gly Uncertain significance ★ ⚠ same type
DBX2 p.Ala12Gly Uncertain significance ★ ⚠ same type
DBX2 p.Ala150Thr Uncertain significance ★ ⚠ same type
DBX2 p.Ala21Pro Uncertain significance ★ ⚠ same type
DBX2 p.Ala28Thr Uncertain significance ★ ⚠ same type
DBX2 p.Ala309Thr 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/dbx2-p-arg184trp (accessed [today's date]).

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