Is DBN1 p.Arg372Trp (c.1114C>T) pathogenic?

DBN1 p.Arg372Trp (c.1114C>T) is classified Uncertain significance in DBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.2136); Ultra-rare (popmax 0.0385%, sas).

How common is DBN1 p.Arg372Trp (c.1114C>T) in the general population?

DBN1 p.Arg372Trp (c.1114C>T) is ultra-rare (popmax 0.0385%, sas) (gnomAD).

What do computational predictors say about DBN1 p.Arg372Trp (c.1114C>T)?

AlphaMissense predicts likely benign (score 0.2136) — an in-silico prediction, not a clinical call.

DBN1 p.Arg372Trp

c.1114C>T · rs377045843 · VCV3080189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2136 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0385%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2136	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -8.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.84 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 R326W vs ClinVar R372W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0385% South Asian · 35/91,024 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00448% 72/1,608,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0385%	2,601
East Asian	0.00671%	14,913
African / African-American	0.00267%	37,391
European (non-Finnish)	0.00263%	38,038
Remaining individualsnot grpmax-eligible	0.0016%	62,344

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: DBN1
Protein: p.Arg372Trp
Coding: c.1114C>T
MANE Select: NM_001363541
dbSNP: rs377045843
Type: single nucleotide variant
Location: chr5:177459248 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93 · 5 PDB
Residue 372: the 'disordered' region

Full DBN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/dbn1-p-arg372trp (accessed [today's date]).

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