Is DBNDD2 p.Glu43Gln (c.127G>C) pathogenic?

DBNDD2 p.Glu43Gln (c.127G>C) is classified Uncertain significance in DBNDD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-27). AlphaMissense: likely benign (0.2693); Very rare (popmax 0.000509%, nfe).

How common is DBNDD2 p.Glu43Gln (c.127G>C) in the general population?

DBNDD2 p.Glu43Gln (c.127G>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about DBNDD2 p.Glu43Gln (c.127G>C)?

AlphaMissense predicts likely benign (score 0.2693) — an in-silico prediction, not a clinical call.

DBNDD2 p.Glu43Gln

c.127G>C · VCV4009506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2693	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.45	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,669 bp · p 0.4 · regional, not allelic
Overall
CADD	27.5	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 E141Q vs ClinVar E43Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,224 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,072 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: DBNDD2
Protein: p.Glu43Gln
Coding: c.127G>C
MANE Select: NM_001048225
Type: single nucleotide variant
Location: chr20:45408594 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 60.09
Residue 43: the 'disordered' region

Full DBNDD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBNDD2 p.Glu43Lys Uncertain significance ★ ⚠ same residue
DBNDD2 c.78G>T Uncertain significance ★ same type
DBNDD2 c.95C>A Uncertain significance ★ same type
DBNDD2 c.-146C>T Uncertain significance ★ same type
DBNDD2 c.-15C>A Uncertain significance ★ ⚠ same type
DBNDD2 c.-29G>T Uncertain significance ★ ⚠ same type
DBNDD2 c.-32C>T Uncertain significance ★ ⚠ same type
DBNDD2 c.-5C>A 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/dbndd2-p-glu43gln (accessed [today's date]).

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