Is DBN1 p.Pro415Gln (c.1244C>A) pathogenic?

DBN1 p.Pro415Gln (c.1244C>A) is classified Uncertain significance in DBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). AlphaMissense: likely benign (0.0678); Very rare (popmax 8.49e-05%, nfe).

How common is DBN1 p.Pro415Gln (c.1244C>A) in the general population?

DBN1 p.Pro415Gln (c.1244C>A) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about DBN1 p.Pro415Gln (c.1244C>A)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

DBN1 p.Pro415Gln

c.1244C>A · rs34692220 · VCV3080175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -9.59	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 5.7	GERP 0.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.84 · regional, not allelic
Overall
CADD	21.2	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 P369Q vs ClinVar P415Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,180 alleles

Overall 6.86e-05% 1/1,457,644 alleles · very rare

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.Pro415Gln
Coding: c.1244C>A
MANE Select: NM_001363541
dbSNP: rs34692220
Type: single nucleotide variant
Location: chr5:177459118 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93 · 5 PDB
Residue 415: the 'disordered' region

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

Similar variants

DBN1 p.Pro415Ser Uncertain significance ★ ⚠ same residue
DBN1 c.86+1283G>A Uncertain significance ★ same type
DBN1 c.86+1286G>A Uncertain significance ★ same type
DBN1 c.86+1299A>T Uncertain significance ★ same type
DBN1 p.Ala126Val Uncertain significance ★ ⚠ same type
DBN1 p.Ala244Val Uncertain significance ★ ⚠ same type
DBN1 p.Ala27Thr Uncertain significance ★ ⚠ same type
DBN1 p.Ala455Val 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/dbn1-p-pro415gln (accessed [today's date]).

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