Is DACT1 p.Cys207= (c.621C>T) pathogenic?

DACT1 p.Cys207= (c.621C>T) is classified Likely benign in DACT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-14). Ultra-rare (popmax 0.0176%, nfe); Associated with DACT1-related disorder.

What condition is associated with DACT1 p.Cys207= (c.621C>T)?

DACT1 p.Cys207= (c.621C>T) is associated with DACT1-related disorder (ClinVar).

How common is DACT1 p.Cys207= (c.621C>T) in the general population?

DACT1 p.Cys207= (c.621C>T) is ultra-rare (popmax 0.0176%, nfe) (gnomAD).

DACT1 p.Cys207=

c.621C>T · rs144708680 · VCV3051835

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, nfe)

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 0.4	GERP -2.3, phastCons 0.98
Overall
CADD	6.919	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% European (non-Finnish) · 208/1,179,868 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.0139% 224/1,613,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0176%	5,672
Middle Eastern	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0144%	6,940
African / African-American	0.00401%	24,947
South Asian	0.0022%	45,357
Admixed American	0.00167%	59,770

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.Cys207=
Coding: c.621C>T
MANE Select: NM_001079520
dbSNP: rs144708680
Type: single nucleotide variant
Location: chr14:58641734 (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.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.Arg659= Likely benign same condition
DACT1 p.Asn336= 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-cys207 (accessed [today's date]).

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