Is DACT1 p.Val339= (c.1017T>C) pathogenic?

DACT1 p.Val339= (c.1017T>C) is classified Likely benign in DACT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-13). Rare (popmax 0.257%, afr); Associated with DACT1-related disorder.

What condition is associated with DACT1 p.Val339= (c.1017T>C)?

DACT1 p.Val339= (c.1017T>C) is associated with DACT1-related disorder (ClinVar).

How common is DACT1 p.Val339= (c.1017T>C) in the general population?

DACT1 p.Val339= (c.1017T>C) is rare (popmax 0.257%, afr) (gnomAD).

DACT1 p.Val339=

c.1017T>C · rs145747677 · VCV3049750

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.257%, afr)

Conditions

DACT1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -4.4, phastCons 0.036
Overall
CADD	2.984	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.257% African / African-American · 193/75,042 alleles

Filtering AF 0.227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.216%

Overall 0.0134% 216/1,614,210 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.257%	389
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.00666%	15,008
European (non-Finnish)	0.000424%	236,008

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: DACT1
Protein: p.Val339=
Coding: c.1017T>C
MANE Select: NM_001079520
dbSNP: rs145747677
Type: single nucleotide variant
Location: chr14:58645751 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 50.95

Full DACT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DACT1-related disorder

Similar variants

DACT1 p.Val339Gly Uncertain significance ★ ⚠ same residue
DACT1 p.Val339Leu Uncertain significance ★ ⚠ same residue
DACT1 p.Ala9Pro Uncertain significance ★ ⚠ same condition
DACT1 p.His426Arg Uncertain significance ★ ⚠ same condition
DACT1 p.Pro295Ala Uncertain significance ★ ⚠ same condition
DACT1 p.Ala677Ser Uncertain significance ⚠ same condition
DACT1 p.Arg85Ser Uncertain significance ⚠ same condition
DACT1 p.Gly560Cys Uncertain significance ⚠ same condition

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/dact1-p-val339 (accessed [today's date]).

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