Is DBX2 p.Ile279Val (c.835A>G) pathogenic?

DBX2 p.Ile279Val (c.835A>G) is classified Uncertain significance in DBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.0626); Rare (popmax 0.214%, mid).

How common is DBX2 p.Ile279Val (c.835A>G) in the general population?

DBX2 p.Ile279Val (c.835A>G) is rare (popmax 0.214%, mid) (gnomAD).

What do computational predictors say about DBX2 p.Ile279Val (c.835A>G)?

AlphaMissense predicts likely benign (score 0.0626) — an in-silico prediction, not a clinical call.

DBX2 p.Ile279Val

c.835A>G · rs146666533 · VCV2342614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0626 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0626	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -5.08	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 -0.18	GERP -5
Regional constraint	o/e 1.24	unconstrained · MANE · 35 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	0.371	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 0.214% Middle Eastern · 13/6,078 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.1%

Overall 0.0169% 273/1,613,796 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.24%	417
Middle Easterngrpmax	0.214%	468
Remaining individualsnot grpmax-eligible	0.0272%	3,675
Admixed American	0.0167%	5,996
European (non-Finnish)	0.0132%	7,564
African / African-American	0.00534%	18,723
Finnishnot grpmax-eligible	0.00156%	64,016
South Asian	0.0011%	91,060

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile279Val
Coding: c.835A>G
MANE Select: NM_001004329
dbSNP: rs146666533
Type: single nucleotide variant
Location: chr12:45016471 (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-ile279val (accessed [today's date]).

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