Is DMBX1 p.Arg362Trp (c.1084C>T) pathogenic?

DMBX1 p.Arg362Trp (c.1084C>T) is classified Uncertain significance in DMBX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: likely pathogenic (0.994); Ultra-rare (popmax 0.0117%, amr).

How common is DMBX1 p.Arg362Trp (c.1084C>T) in the general population?

DMBX1 p.Arg362Trp (c.1084C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about DMBX1 p.Arg362Trp (c.1084C>T)?

AlphaMissense predicts likely pathogenic (score 0.994) — an in-silico prediction, not a clinical call.

DMBX1 p.Arg362Trp

c.1084C>T · rs756762775 · VCV2244691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.994	likely pathogenic
REVEL	0.769	pathogenic-leaning
SaProt	LLR -12.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.86, phastCons 0.97
Regional constraint	o/e 0.97	unconstrained · MANE · 1,541 bp · p 0.55 · regional, not allelic
Overall
CADD	28.3	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R367W vs ClinVar R362W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,998 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00242% 39/1,613,624 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
African / African-American	0.004%	24,971
East Asian	0.00223%	44,888
South Asian	0.0022%	45,539
European (non-Finnish)	0.00212%	47,196
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: DMBX1
Protein: p.Arg362Trp
Coding: c.1084C>T
MANE Select: NM_172225
dbSNP: rs756762775
Type: single nucleotide variant
Location: chr1:46512444 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.71

Full DMBX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMBX1 c.155-10A>T Uncertain significance ★ ⚠ same type
DMBX1 p.Ala213Val Uncertain significance ★ ⚠ same type
DMBX1 p.Ala239Val Uncertain significance ★ ⚠ same type
DMBX1 p.Ala27Ser Uncertain significance ★ ⚠ same type
DMBX1 p.Ala291Thr Uncertain significance ★ ⚠ same type
DMBX1 p.Ala295Thr Uncertain significance ★ ⚠ same type
DMBX1 p.Ala367Ser Uncertain significance ★ ⚠ same type
DMBX1 p.Ala367Thr 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/dmbx1-p-arg362trp (accessed [today's date]).

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