Is DACT2 p.Glu683Lys (c.2047G>A) pathogenic?

DACT2 p.Glu683Lys (c.2047G>A) is classified Uncertain significance in DACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-13). AlphaMissense: likely benign (0.0977); Ultra-rare (popmax 0.0196%, eas).

How common is DACT2 p.Glu683Lys (c.2047G>A) in the general population?

DACT2 p.Glu683Lys (c.2047G>A) is ultra-rare (popmax 0.0196%, eas) (gnomAD).

What do computational predictors say about DACT2 p.Glu683Lys (c.2047G>A)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

DACT2 p.Glu683Lys

c.2047G>A · rs1202698562 · VCV2223648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -10.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.7, phastCons 0.059
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.68 · regional, not allelic
Overall
CADD	23.2	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 0.0196% East Asian · 8/40,898 alleles

Filtering AF 0.00968% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00704%

Overall 0.00148% 23/1,550,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0196%	5,112
Admixed American	0.0118%	8,498
Remaining individualsnot grpmax-eligible	0.00333%	30,038
Finnishnot grpmax-eligible	0.00171%	58,568
South Asian	0.00119%	84,038
European (non-Finnish)	0.000436%	229,377

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.Glu683Lys
Coding: c.2047G>A
MANE Select: NM_214462
dbSNP: rs1202698562
Type: single nucleotide variant
Location: chr6:168307710 (GRCh38)
Gene constraint: LOEUF 1.469 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.81
Residue 683: the 'disordered' region

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

Similar variants

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
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-glu683lys (accessed [today's date]).

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