Is DBX2 p.Trp14Ser (c.41G>C) pathogenic?

DBX2 p.Trp14Ser (c.41G>C) is classified Uncertain significance in DBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: ambiguous (0.5041); Very rare (popmax 0.00527%, nfe).

How common is DBX2 p.Trp14Ser (c.41G>C) in the general population?

DBX2 p.Trp14Ser (c.41G>C) is very rare (popmax 0.00527%, nfe) (gnomAD).

What do computational predictors say about DBX2 p.Trp14Ser (c.41G>C)?

AlphaMissense predicts ambiguous (score 0.5041) — an in-silico prediction, not a clinical call.

DBX2 p.Trp14Ser

c.41G>C · VCV4009533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00527%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5041	ambiguous
REVEL	0.572	indeterminate
SaProt	LLR -5.32	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.9, phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 35 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	25.6	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 0.00527% European (non-Finnish) · 60/1,138,298 alleles

Filtering AF 0.00417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00414% 63/1,523,272 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00527%	18,972
African / African-American	0.00286%	35,013
Remaining individualsnot grpmax-eligible	0.0017%	58,738

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.Trp14Ser
Coding: c.41G>C
MANE Select: NM_001004329
Type: single nucleotide variant
Location: chr12:45050887 (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-trp14ser (accessed [today's date]).

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