Is DBX1 p.Pro9Thr (c.25C>A) pathogenic?

DBX1 p.Pro9Thr (c.25C>A) is classified Uncertain significance in DBX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1364); Very rare (popmax 8.78e-05%, nfe).

How common is DBX1 p.Pro9Thr (c.25C>A) in the general population?

DBX1 p.Pro9Thr (c.25C>A) is very rare (popmax 8.78e-05%, nfe) (gnomAD).

What do computational predictors say about DBX1 p.Pro9Thr (c.25C>A)?

AlphaMissense predicts likely benign (score 0.1364) — an in-silico prediction, not a clinical call.

DBX1 p.Pro9Thr

c.25C>A · VCV4237766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.78e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1364	likely benign
REVEL	0.582	indeterminate
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,107 bp · p 0.095 · regional, not allelic
Overall
CADD	25.1	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 8.78e-05% European (non-Finnish) · 1/1,138,640 alleles

Overall 7.28e-05% 1/1,373,882 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: DBX1
Protein: p.Pro9Thr
Coding: c.25C>A
MANE Select: NM_001029865
Type: single nucleotide variant
Location: chr11:20160300 (GRCh38)
Gene constraint: LOEUF 0.98 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.03

Full DBX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBX1 p.Ala127Pro Uncertain significance ★ ⚠ same type
DBX1 p.Ala127Val Uncertain significance ★ ⚠ same type
DBX1 p.Ala314Thr Uncertain significance ★ ⚠ same type
DBX1 p.Ala314Val Uncertain significance ★ ⚠ same type
DBX1 p.Arg211Leu Uncertain significance ★ ⚠ same type
DBX1 p.Arg237Trp Uncertain significance ★ ⚠ same type
DBX1 p.Arg49Pro Uncertain significance ★ ⚠ same type
DBX1 p.Arg56Ser 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/dbx1-p-pro9thr (accessed [today's date]).

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