Is DACT2 p.Arg44Pro (c.131G>C) pathogenic?

DACT2 p.Arg44Pro (c.131G>C) is classified Uncertain significance in DACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.7619); Ultra-rare (popmax 0.0462%, amr).

How common is DACT2 p.Arg44Pro (c.131G>C) in the general population?

DACT2 p.Arg44Pro (c.131G>C) is ultra-rare (popmax 0.0462%, amr) (gnomAD).

What do computational predictors say about DACT2 p.Arg44Pro (c.131G>C)?

AlphaMissense predicts likely pathogenic (score 0.7619) — an in-silico prediction, not a clinical call.

DACT2 p.Arg44Pro

c.131G>C · rs1441818728 · VCV3079956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7619 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0462%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7619	likely pathogenic · top 7% in DACT2
REVEL	0.202	benign-leaning
SaProt	LLR -14.19	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.68 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.0462% Admixed American · 16/34,606 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0236%

Overall 0.00778% 102/1,311,278 alleles · ultra-rare exomes 84/1,160,204 · genomes 18/151,074 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0462%	2,163
Remaining individualsnot grpmax-eligible	0.0126%	7,935
European (non-Finnish)	0.00772%	12,958
African / African-American	0.00153%	65,374

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: DACT2
Protein: p.Arg44Pro
Coding: c.131G>C
MANE Select: NM_214462
dbSNP: rs1441818728
Type: single nucleotide variant
Location: chr6:168319503 (GRCh38)
Gene constraint: LOEUF 1.469 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.81

Full DACT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DACT2 p.Arg44Gly Uncertain significance ★ ⚠ same residue
DACT2 p.Ala11Thr Uncertain significance ★ ⚠ same type
DACT2 p.Ala162Thr Uncertain significance ★ ⚠ same type
DACT2 p.Ala186Val Uncertain significance ★ ⚠ same type
DACT2 p.Ala228Val Uncertain significance ★ ⚠ same type
DACT2 p.Ala239Thr Uncertain significance ★ ⚠ same type
DACT2 p.Ala283Val Uncertain significance ★ ⚠ same type
DACT2 p.Ala312Thr 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/dact2-p-arg44pro (accessed [today's date]).

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