Is DACT2 p.Arg44Gly (c.130C>G) pathogenic?

DACT2 p.Arg44Gly (c.130C>G) is classified Uncertain significance in DACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.2269); Very rare (popmax 0.00674%, eas).

How common is DACT2 p.Arg44Gly (c.130C>G) in the general population?

DACT2 p.Arg44Gly (c.130C>G) is very rare (popmax 0.00674%, eas) (gnomAD).

What do computational predictors say about DACT2 p.Arg44Gly (c.130C>G)?

AlphaMissense predicts likely benign (score 0.2269) — an in-silico prediction, not a clinical call.

DACT2 p.Arg44Gly

c.130C>G · rs1431459784 · VCV2234082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00674%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2269	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -9.31	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 -0.22, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.68 · regional, not allelic
Overall
CADD	22.0	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 0.00674% East Asian · 2/29,678 alleles

Filtering AF 0.00112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000417%

Overall 0.000303% 4/1,320,182 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00674%	14,839
South Asian	0.00192%	52,062
European (non-Finnish)	9.73e-05%	1,027,978

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: DACT2
Protein: p.Arg44Gly
Coding: c.130C>G
MANE Select: NM_214462
dbSNP: rs1431459784
Type: single nucleotide variant
Location: chr6:168319504 (GRCh38)
Gene constraint: LOEUF 1.469 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.81

Full DACT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DACT2 p.Arg44Pro Uncertain significance ★ ⚠ same residue
DACT2 p.Ala11Thr Uncertain significance ★ ⚠ same type
DACT2 p.Ala162Thr Uncertain significance ★ ⚠ same type
DACT2 p.Ala186Val Uncertain significance ★ ⚠ same type
DACT2 p.Ala228Val Uncertain significance ★ ⚠ same type
DACT2 p.Ala239Thr Uncertain significance ★ ⚠ same type
DACT2 p.Ala283Val Uncertain significance ★ ⚠ same type
DACT2 p.Ala312Thr 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/dact2-p-arg44gly (accessed [today's date]).

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