Is DBX2 p.Asp113Glu (c.339C>G) pathogenic?

DBX2 p.Asp113Glu (c.339C>G) is classified Uncertain significance in DBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely benign (0.1082); Very rare (popmax 0.00119%, sas).

How common is DBX2 p.Asp113Glu (c.339C>G) in the general population?

DBX2 p.Asp113Glu (c.339C>G) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about DBX2 p.Asp113Glu (c.339C>G)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

DBX2 p.Asp113Glu

c.339C>G · rs1946525681 · VCV2225834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -6.15	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 1.3	GERP -1.9, phastCons 0.04
Regional constraint	o/e 1.24	unconstrained · MANE · 35 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	10.38	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 0.00119% South Asian · 1/84,142 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000286% 4/1,399,578 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,142
European (non-Finnish)	0.000261%	382,717

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.Asp113Glu
Coding: c.339C>G
MANE Select: NM_001004329
dbSNP: rs1946525681
Type: single nucleotide variant
Location: chr12:45050589 (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-asp113glu (accessed [today's date]).

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