Is DBX2 p.Gln72His (c.216G>C) pathogenic?

DBX2 p.Gln72His (c.216G>C) is classified Uncertain significance in DBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.1125); Very rare (popmax 8.88e-05%, nfe).

How common is DBX2 p.Gln72His (c.216G>C) in the general population?

DBX2 p.Gln72His (c.216G>C) is very rare (popmax 8.88e-05%, nfe) (gnomAD).

What do computational predictors say about DBX2 p.Gln72His (c.216G>C)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

DBX2 p.Gln72His

c.216G>C · VCV4009538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.88e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -6.11	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 0.94	GERP -2.7, phastCons 0.98
Regional constraint	o/e 1.24	unconstrained · MANE · 35 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	14.93	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 8.88e-05% European (non-Finnish) · 1/1,126,374 alleles

Overall 7.43e-05% 1/1,346,420 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: DBX2
Protein: p.Gln72His
Coding: c.216G>C
MANE Select: NM_001004329
Type: single nucleotide variant
Location: chr12:45050712 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.74

Full DBX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBX2 p.Arg267= Benign ★★ same type
DBX2 p.Ala104Val Uncertain significance ★ ⚠ same type
DBX2 p.Ala10Gly Uncertain significance ★ ⚠ same type
DBX2 p.Ala12Gly Uncertain significance ★ ⚠ same type
DBX2 p.Ala150Thr Uncertain significance ★ ⚠ same type
DBX2 p.Ala21Pro Uncertain significance ★ ⚠ same type
DBX2 p.Ala28Thr Uncertain significance ★ ⚠ same type
DBX2 p.Ala309Thr 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/dbx2-p-gln72his (accessed [today's date]).

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