Is DBN1 p.Arg149Gln (c.446G>A) pathogenic?

DBN1 p.Arg149Gln (c.446G>A) is classified Uncertain significance in DBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.2217); Ultra-rare (popmax 0.0358%, amr).

How common is DBN1 p.Arg149Gln (c.446G>A) in the general population?

DBN1 p.Arg149Gln (c.446G>A) is ultra-rare (popmax 0.0358%, amr) (gnomAD).

What do computational predictors say about DBN1 p.Arg149Gln (c.446G>A)?

AlphaMissense predicts likely benign (score 0.2217) — an in-silico prediction, not a clinical call.

DBN1 p.Arg149Gln

c.446G>A · rs758971267 · VCV2377773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2217 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0358%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2217	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.29	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 302 bp · p 0.0011 · regional, not allelic
Overall
CADD	23.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0358% Admixed American · 19/53,030 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0195%

Overall 0.00299% 47/1,574,432 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0358%	2,791
European (non-Finnish)	0.00224%	44,599
Remaining individualsnot grpmax-eligible	0.00164%	60,982
African / African-American	0.00135%	73,876

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.Arg149Gln
Coding: c.446G>A
MANE Select: NM_001363541
dbSNP: rs758971267
Type: single nucleotide variant
Location: chr5:177467512 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93 · 5 PDB

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

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DBN1 p.Ala126Val Uncertain significance ★ ⚠ same type
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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-arg149gln (accessed [today's date]).

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