Is DACT1 p.Pro295Ala (c.883C>G) pathogenic?

DACT1 p.Pro295Ala (c.883C>G) is classified Uncertain significance in DACT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely benign (0.083); Absent from gnomAD v4.1; Associated with DACT1-related disorder.

What condition is associated with DACT1 p.Pro295Ala (c.883C>G)?

DACT1 p.Pro295Ala (c.883C>G) is associated with DACT1-related disorder (ClinVar).

How common is DACT1 p.Pro295Ala (c.883C>G) in the general population?

DACT1 p.Pro295Ala (c.883C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DACT1 p.Pro295Ala (c.883C>G)?

AlphaMissense predicts likely benign (score 0.083) — an in-silico prediction, not a clinical call.

DACT1 p.Pro295Ala

c.883C>G · rs1205762805 · VCV2631317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.083 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DACT1-related disorder

Computational evidence

Protein change
AlphaMissense	0.083	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.2, phastCons 0.77
Regional constraint	o/e 1.10	unconstrained · MANE · 8,733 bp · p 0.0021 · regional, not allelic
Overall
CADD	18.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P332A vs ClinVar P295A) — verify the residue.

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.Pro295Ala
Coding: c.883C>G
MANE Select: NM_001079520
dbSNP: rs1205762805
Type: single nucleotide variant
Location: chr14:58645617 (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.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
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-pro295ala (accessed [today's date]).

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