Is DACT1 p.Arg659= (c.1977C>T) pathogenic?

DACT1 p.Arg659= (c.1977C>T) is classified Likely benign in DACT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-22). Ultra-rare (popmax 0.0681%, sas); Associated with DACT1-related disorder.

What condition is associated with DACT1 p.Arg659= (c.1977C>T)?

DACT1 p.Arg659= (c.1977C>T) is associated with DACT1-related disorder (ClinVar).

How common is DACT1 p.Arg659= (c.1977C>T) in the general population?

DACT1 p.Arg659= (c.1977C>T) is ultra-rare (popmax 0.0681%, sas) (gnomAD).

DACT1 p.Arg659=

c.1977C>T · rs147992151 · VCV3058180

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, sas)

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 -2.3	GERP -5.2
Overall
CADD	4.211	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0681% South Asian · 62/91,072 alleles

Filtering AF 0.0544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0495%

Overall 0.0121% 196/1,613,280 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0681%	1,469
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)	0.0103%	9,672
Finnishnot grpmax-eligible	0.00158%	63,336
African / African-American	0.00133%	75,034

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.Arg659=
Coding: c.1977C>T
MANE Select: NM_001079520
dbSNP: rs147992151
Type: single nucleotide variant
Location: chr14:58646711 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 50.95
Residue 659: a UniProt-annotated variant site (in tbs2; the mutant protein is stable and expressed); the 'disordered' region

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

Disease context

DACT1-related disorder

Similar variants

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
DACT1 p.Asn336= Likely benign same condition
DACT1 p.Cys207= Likely benign 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-arg659 (accessed [today's date]).

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