Is DACT2 p.Glu704Lys (c.2110G>A) pathogenic?

DACT2 p.Glu704Lys (c.2110G>A) is classified Uncertain significance in DACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). AlphaMissense: likely benign (0.0906); Very rare (popmax 0.00821%, afr).

How common is DACT2 p.Glu704Lys (c.2110G>A) in the general population?

DACT2 p.Glu704Lys (c.2110G>A) is very rare (popmax 0.00821%, afr) (gnomAD).

What do computational predictors say about DACT2 p.Glu704Lys (c.2110G>A)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

DACT2 p.Glu704Lys

c.2110G>A · rs376125439 · VCV2552883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00821%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -9.04	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 -0.44	GERP -3.5
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.68 · regional, not allelic
Overall
CADD	8.566	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 0.00821% African / African-American · 6/73,100 alleles

Filtering AF 0.00354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00207% 32/1,547,498 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00821%	12,183
European (non-Finnish)	0.00218%	45,776
South Asian	0.0012%	83,660

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.Glu704Lys
Coding: c.2110G>A
MANE Select: NM_214462
dbSNP: rs376125439
Type: single nucleotide variant
Location: chr6:168307647 (GRCh38)
Gene constraint: LOEUF 1.469 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.81
Residue 704: the 'disordered' region

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

Similar variants

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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
DACT2 p.Ala332Thr 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-glu704lys (accessed [today's date]).

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