Is DACT3 p.Ala4Thr (c.10G>A) pathogenic?

DACT3 p.Ala4Thr (c.10G>A) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: likely pathogenic (0.9381); Very rare (popmax 0.00838%, eas).

How common is DACT3 p.Ala4Thr (c.10G>A) in the general population?

DACT3 p.Ala4Thr (c.10G>A) is very rare (popmax 0.00838%, eas) (gnomAD).

What do computational predictors say about DACT3 p.Ala4Thr (c.10G>A)?

AlphaMissense predicts likely pathogenic (score 0.9381) — an in-silico prediction, not a clinical call.

DACT3 p.Ala4Thr

c.10G>A · VCV3838178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9381 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00838%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9381	likely pathogenic
REVEL	0.17	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 11 kb · p 4.5e-05 · regional, not allelic
Overall
CADD	29.5	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 0.00838% East Asian · 3/35,792 alleles

Filtering AF 0.00222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00122%

Overall 0.000268% 4/1,494,666 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00838%	11,931
African / African-American	0.00146%	68,720

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.Ala4Thr
Coding: c.10G>A
MANE Select: NM_145056
Type: single nucleotide variant
Location: chr19:46661055 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51

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

Similar variants

DACT3 p.Ala4Gly Uncertain significance ★ ⚠ same residue
DACT3 p.Ala179Pro Uncertain significance ★ ⚠ same type
DACT3 p.Ala181Ser Uncertain significance ★ ⚠ same type
DACT3 p.Ala181Thr Uncertain significance ★ ⚠ same type
DACT3 p.Ala194Thr 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

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-ala4thr (accessed [today's date]).

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