Is DACT1 p.Asn253Ser (c.758A>G) pathogenic?

DACT1 p.Asn253Ser (c.758A>G) is classified Uncertain significance in DACT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: likely benign (0.065); Absent from gnomAD v4.1.

How common is DACT1 p.Asn253Ser (c.758A>G) in the general population?

DACT1 p.Asn253Ser (c.758A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DACT1 p.Asn253Ser (c.758A>G)?

AlphaMissense predicts likely benign (score 0.065) — an in-silico prediction, not a clinical call.

DACT1 p.Asn253Ser

c.758A>G · rs1475886511 · VCV3079952

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.065 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.065	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -4.76	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 -0.5	GERP -5
Regional constraint	o/e 1.10	unconstrained · MANE · 8,733 bp · p 0.0021 · regional, not allelic
Overall
CADD	1.361	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 N290S vs ClinVar N253S) — 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.Asn253Ser
Coding: c.758A>G
MANE Select: NM_001079520
dbSNP: rs1475886511
Type: single nucleotide variant
Location: chr14:58645492 (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

Similar variants

DACT1 p.Glu451Asp Uncertain significance ★★ ⚠ same type
DACT1 c.635-121T>C Likely benign ★★ same type
DACT1 p.Ala427Val Benign ★★ same type
DACT1 p.Ala500= Benign ★★ same type
DACT1 p.Asp409Asn Benign ★★ same type
DACT1 p.Glu257Lys Benign/Likely benign ★★ same type
DACT1 p.Glu49= Likely benign ★★ same type
DACT1 p.Gly660Ser Benign ★★ same type

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-asn253ser (accessed [today's date]).

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