Is DACT3 p.Ala194Thr (c.580G>A) pathogenic?

DACT3 p.Ala194Thr (c.580G>A) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-30). AlphaMissense: likely benign (0.0939); Very rare (popmax 9.43e-05%, nfe).

How common is DACT3 p.Ala194Thr (c.580G>A) in the general population?

DACT3 p.Ala194Thr (c.580G>A) is very rare (popmax 9.43e-05%, nfe) (gnomAD).

What do computational predictors say about DACT3 p.Ala194Thr (c.580G>A)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

DACT3 p.Ala194Thr

c.580G>A · VCV3838181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.43e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -7.88	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 7.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 11 kb · p 4.5e-05 · regional, not allelic
Overall
CADD	24.2	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 9.43e-05% European (non-Finnish) · 1/1,059,922 alleles

Overall 8.28e-05% 1/1,207,708 alleles · very rare

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: DACT3
Protein: p.Ala194Thr
Coding: c.580G>A
MANE Select: NM_145056
Type: single nucleotide variant
Location: chr19:46649792 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51
Residue 194: the 'disordered' region

Full DACT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DACT3 p.Ala179Pro Uncertain significance ★ ⚠ same type
DACT3 p.Ala181Ser Uncertain significance ★ ⚠ same type
DACT3 p.Ala181Thr Uncertain significance ★ ⚠ same type
DACT3 p.Ala299Gly Uncertain significance ★ ⚠ same type
DACT3 p.Ala318Ser Uncertain significance ★ ⚠ same type
DACT3 p.Ala338Pro Uncertain significance ★ ⚠ same type
DACT3 p.Ala363Val Uncertain significance ★ ⚠ same type
DACT3 p.Ala365Thr 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/dact3-p-ala194thr (accessed [today's date]).

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