Is DACT3 p.Asp250Asn (c.748G>A) pathogenic?

DACT3 p.Asp250Asn (c.748G>A) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.5766); Ultra-rare (popmax 0.0358%, eas).

How common is DACT3 p.Asp250Asn (c.748G>A) in the general population?

DACT3 p.Asp250Asn (c.748G>A) is ultra-rare (popmax 0.0358%, eas) (gnomAD).

What do computational predictors say about DACT3 p.Asp250Asn (c.748G>A)?

AlphaMissense predicts likely pathogenic (score 0.5766) — an in-silico prediction, not a clinical call.

DACT3 p.Asp250Asn

c.748G>A · VCV3838172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0358%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5766	likely pathogenic
REVEL	0.132	moderately benign-leaning
SaProt	LLR -7.79	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 5.2	GERP -1.8, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,201 bp · p 0.027 · regional, not allelic
Overall
CADD	24.2	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 0.0358% East Asian · 7/19,530 alleles

Filtering AF 0.0168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00124% 14/1,132,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0358%	2,790
Remaining individualsnot grpmax-eligible	0.0184%	5,439

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.Asp250Asn
Coding: c.748G>A
MANE Select: NM_145056
Type: single nucleotide variant
Location: chr19:46649624 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51
Residue 250: 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.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
DACT3 p.Ala363Val 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-asp250asn (accessed [today's date]).

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