Is DACT3 p.Pro268Thr (c.802C>A) pathogenic?

DACT3 p.Pro268Thr (c.802C>A) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely pathogenic (0.5902); Rare (popmax 0.256%, eas).

How common is DACT3 p.Pro268Thr (c.802C>A) in the general population?

DACT3 p.Pro268Thr (c.802C>A) is rare (popmax 0.256%, eas) (gnomAD).

What do computational predictors say about DACT3 p.Pro268Thr (c.802C>A)?

AlphaMissense predicts likely pathogenic (score 0.5902) — an in-silico prediction, not a clinical call.

DACT3 p.Pro268Thr

c.802C>A · rs189187210 · VCV2213171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5902 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.256%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5902	likely pathogenic
REVEL	0.205	benign-leaning
SaProt	LLR -7.77	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 10	GERP -0.41, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,201 bp · p 0.027 · regional, not allelic
Overall
CADD	25.3	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 0.256% East Asian · 32/12,496 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.00379% 41/1,080,394 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.256%	390
Remaining individualsnot grpmax-eligible	0.00291%	34,358
European (non-Finnish)	0.0009%	111,102

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.Pro268Thr
Coding: c.802C>A
MANE Select: NM_145056
dbSNP: rs189187210
Type: single nucleotide variant
Location: chr19:46649570 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51
Residue 268: 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-pro268thr (accessed [today's date]).

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