Is DACT2 p.Glu423Lys (c.1267G>A) pathogenic?

DACT2 p.Glu423Lys (c.1267G>A) is classified Uncertain significance in DACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.0818); Absent from gnomAD v4.1.

How common is DACT2 p.Glu423Lys (c.1267G>A) in the general population?

DACT2 p.Glu423Lys (c.1267G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DACT2 p.Glu423Lys (c.1267G>A)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

DACT2 p.Glu423Lys

c.1267G>A · VCV4658400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.13	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 -0.092	GERP -2.1
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.68 · regional, not allelic
Overall
CADD	13.23	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DACT2
Protein: p.Glu423Lys
Coding: c.1267G>A
MANE Select: NM_214462
Type: single nucleotide variant
Location: chr6:168308490 (GRCh38)
Gene constraint: LOEUF 1.469 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.81
Residue 423: 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-glu423lys (accessed [today's date]).

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