Is DBX2 p.Pro94Ala (c.280C>G) pathogenic?

DBX2 p.Pro94Ala (c.280C>G) is classified Uncertain significance in DBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.0562); Rare (popmax 0.448%, nfe).

How common is DBX2 p.Pro94Ala (c.280C>G) in the general population?

DBX2 p.Pro94Ala (c.280C>G) is rare (popmax 0.448%, nfe) (gnomAD).

What do computational predictors say about DBX2 p.Pro94Ala (c.280C>G)?

AlphaMissense predicts likely benign (score 0.0562) — an in-silico prediction, not a clinical call.

DBX2 p.Pro94Ala

c.280C>G · VCV4237780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0562 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.448%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0562	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -6.33	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 0.6	GERP -1.1, phastCons 0.65
Regional constraint	o/e 1.24	unconstrained · MANE · 35 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	18.83	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 0.448% European (non-Finnish) · 5,141/1,146,836 alleles

Filtering AF 0.438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.434%

Overall 0.361% 5,590/1,549,690 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.448%	223
Remaining individualsnot grpmax-eligible	0.283%	353
Finnishnot grpmax-eligible	0.231%	434
Ashkenazi Jewishnot grpmax-eligible	0.0805%	1,242
Admixed American	0.0803%	1,246
African / African-American	0.0603%	1,658
Middle Eastern	0.0522%	1,914
South Asian	0.0392%	2,548

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.Pro94Ala
Coding: c.280C>G
MANE Select: NM_001004329
Type: single nucleotide variant
Location: chr12:45050648 (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-pro94ala (accessed [today's date]).

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