Is DACT3 p.Cys524Tyr (c.1571G>A) pathogenic?

DACT3 p.Cys524Tyr (c.1571G>A) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: ambiguous (0.5395); Absent from gnomAD v4.1.

How common is DACT3 p.Cys524Tyr (c.1571G>A) in the general population?

DACT3 p.Cys524Tyr (c.1571G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DACT3 p.Cys524Tyr (c.1571G>A)?

AlphaMissense predicts ambiguous (score 0.5395) — an in-silico prediction, not a clinical call.

DACT3 p.Cys524Tyr

c.1571G>A · VCV4237462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5395 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,533,744)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5395	ambiguous
REVEL	0.182	moderately benign-leaning
SaProt	LLR -7.90	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 5.4	GERP -3.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,201 bp · p 0.027 · regional, not allelic
Overall
CADD	23.6	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

No allele count reported in gnomAD v4.1 (AN 1,533,744). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DACT3
Protein: p.Cys524Tyr
Coding: c.1571G>A
MANE Select: NM_145056
Type: single nucleotide variant
Location: chr19:46648801 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51
Residue 524: 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-cys524tyr (accessed [today's date]).

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