Is DBX1 p.Leu6Pro (c.17T>C) pathogenic?

DBX1 p.Leu6Pro (c.17T>C) is classified Uncertain significance in DBX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.3438); Very rare (popmax 0.00496%, eas).

How common is DBX1 p.Leu6Pro (c.17T>C) in the general population?

DBX1 p.Leu6Pro (c.17T>C) is very rare (popmax 0.00496%, eas) (gnomAD).

What do computational predictors say about DBX1 p.Leu6Pro (c.17T>C)?

AlphaMissense predicts ambiguous (score 0.3438) — an in-silico prediction, not a clinical call.

DBX1 p.Leu6Pro

c.17T>C · VCV4237771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3438 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00496%, eas)

Computational evidence

Protein change
AlphaMissense	0.3438	ambiguous
REVEL	0.445	indeterminate
SaProt	LLR -6.97	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,107 bp · p 0.095 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00496% East Asian · 2/40,346 alleles

Filtering AF 0.000821% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000307%

Overall 0.000263% 4/1,521,224 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00496%	20,173
Remaining individualsnot grpmax-eligible	0.0017%	58,918
South Asian	0.00122%	82,248

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.Leu6Pro
Coding: c.17T>C
MANE Select: NM_001029865
Type: single nucleotide variant
Location: chr11:20160308 (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-leu6pro (accessed [today's date]).

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