Is DACT3 p.Arg413His (c.1238G>A) pathogenic?

DACT3 p.Arg413His (c.1238G>A) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: ambiguous (0.4761); Ultra-rare (popmax 0.0126%, afr).

How common is DACT3 p.Arg413His (c.1238G>A) in the general population?

DACT3 p.Arg413His (c.1238G>A) is ultra-rare (popmax 0.0126%, afr) (gnomAD).

What do computational predictors say about DACT3 p.Arg413His (c.1238G>A)?

AlphaMissense predicts ambiguous (score 0.4761) — an in-silico prediction, not a clinical call.

DACT3 p.Arg413His

c.1238G>A · VCV3838175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4761 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4761	ambiguous
REVEL	0.151	moderately benign-leaning
SaProt	LLR -8.43	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP -2.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,201 bp · p 0.027 · regional, not allelic
Overall
CADD	24.5	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 0.0126% African / African-American · 8/63,454 alleles

Filtering AF 0.00621% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0045%

Overall 0.000868% 11/1,267,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0126%	7,932
Admixed American	0.00424%	23,584
Remaining individualsnot grpmax-eligible	0.00218%	45,828
European (non-Finnish)	9.91e-05%	1,008,658

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.Arg413His
Coding: c.1238G>A
MANE Select: NM_145056
Type: single nucleotide variant
Location: chr19:46649134 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51
Residue 413: the 'disordered' region

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

Similar variants

DACT3 p.Arg413Cys 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-arg413his (accessed [today's date]).

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