Is DACT3 p.Cys232Tyr (c.695G>A) pathogenic?

DACT3 p.Cys232Tyr (c.695G>A) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.1244); Ultra-rare (popmax 0.0341%, mid).

How common is DACT3 p.Cys232Tyr (c.695G>A) in the general population?

DACT3 p.Cys232Tyr (c.695G>A) is ultra-rare (popmax 0.0341%, mid) (gnomAD).

What do computational predictors say about DACT3 p.Cys232Tyr (c.695G>A)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

DACT3 p.Cys232Tyr

c.695G>A · rs952358451 · VCV3079985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0341%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -7.20	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 4.2	GERP -1.3, phastCons 0.99
Regional constraint	o/e 1.09	unconstrained · MANE · 1,201 bp · p 0.027 · regional, not allelic
Overall
CADD	14.81	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 0.0341% Middle Eastern · 1/2,930 alleles

Filtering AF 0.00908% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00591%

Overall 0.00722% 85/1,177,428 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0341%	2,930
Admixed American	0.0233%	4,300
African / African-American	0.00973%	10,283
Remaining individualsnot grpmax-eligible	0.00962%	10,397
European (non-Finnish)	0.00713%	14,030
East Asian	0.00384%	26,068

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.Cys232Tyr
Coding: c.695G>A
MANE Select: NM_145056
dbSNP: rs952358451
Type: single nucleotide variant
Location: chr19:46649677 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51
Residue 232: 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-cys232tyr (accessed [today's date]).

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