Is DACT1 p.Leu255= (c.763C>T) pathogenic?

DACT1 p.Leu255= (c.763C>T) is classified Likely pathogenic in DACT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-11-05). Absent from gnomAD v4.1; Associated with Townes-Brocks syndrome 2.

What condition is associated with DACT1 p.Leu255= (c.763C>T)?

DACT1 p.Leu255= (c.763C>T) is associated with Townes-Brocks syndrome 2 (ClinVar).

How common is DACT1 p.Leu255= (c.763C>T) in the general population?

DACT1 p.Leu255= (c.763C>T) is absent from gnomAD v4.1 (gnomAD).

DACT1 p.Leu255=

c.763C>T · VCV3899992

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Townes-Brocks syndrome 2

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 1.1	GERP 1.3, phastCons 0.54
Overall
CADD	8.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DACT1
Protein: p.Leu255=
Coding: c.763C>T
MANE Select: NM_001079520
Type: single nucleotide variant
Location: chr14:58645497 (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

Townes-Brocks syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DACT1 p.Glu451Asp Uncertain significance ★★ ⚠ same condition
DACT1 p.Ala427Val Benign ★★ same condition
DACT1 p.Glu257Lys Benign/Likely benign ★★ same condition
DACT1 p.Leu90= Benign ★★ same condition
DACT1 p.Gln310His Conflicting classifications of pathogenicity ★ same condition
DACT1 p.Glu708Lys Uncertain significance ★ ⚠ same condition
DACT1 p.Gly744Ser Uncertain significance ★ ⚠ same condition
DACT1 p.Phe376Leu 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-leu255 (accessed [today's date]).

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