Is DACT3 p.Leu79Arg (c.236T>G) pathogenic?

DACT3 p.Leu79Arg (c.236T>G) is classified Uncertain significance in DACT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely pathogenic (0.8677); Absent from gnomAD v4.1.

How common is DACT3 p.Leu79Arg (c.236T>G) in the general population?

DACT3 p.Leu79Arg (c.236T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DACT3 p.Leu79Arg (c.236T>G)?

AlphaMissense predicts likely pathogenic (score 0.8677) — an in-silico prediction, not a clinical call.

DACT3 p.Leu79Arg

c.236T>G · rs2513704273 · VCV2527609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8677 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8677	likely pathogenic
REVEL	0.453	indeterminate
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.31, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 11 kb · p 4.5e-05 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

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

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: DACT3
Protein: p.Leu79Arg
Coding: c.236T>G
MANE Select: NM_145056
dbSNP: rs2513704273
Type: single nucleotide variant
Location: chr19:46660829 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 53.51

Full DACT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DACT3 p.Ala179Pro Uncertain significance ★ ⚠ same type
DACT3 p.Ala181Ser Uncertain significance ★ ⚠ same type
DACT3 p.Ala181Thr Uncertain significance ★ ⚠ same type
DACT3 p.Ala194Thr Uncertain significance ★ ⚠ same type
DACT3 p.Ala299Gly Uncertain significance ★ ⚠ same type
DACT3 p.Ala318Ser Uncertain significance ★ ⚠ same type
DACT3 p.Ala338Pro Uncertain significance ★ ⚠ same type
DACT3 p.Ala363Val Uncertain significance ★ ⚠ 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/dact3-p-leu79arg (accessed [today's date]).

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