Is DACT2 p.Gly707= (c.2121C>T) pathogenic?

DACT2 p.Gly707= (c.2121C>T) is classified Benign in DACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-14). Common (popmax 9.76%, eas) — too common for a highly-penetrant pathogenic allele.

DACT2 p.Gly707=

Q: How common is DACT2 p.Gly707= (c.2121C>T) in the general population?

DACT2 p.Gly707= (c.2121C>T) is common (popmax 9.76%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2121C>T · rs78695494 · VCV769702

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 9.76%, eas) — too common for a highly-penetrant pathogenic allele

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 -5.4	GERP -3.5
Overall
CADD	0.714	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.76% East Asian · 3,978/40,748 alleles

Filtering AF 9.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.41%

Overall 0.484% 7,494/1,547,220 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	9.76%	10
Admixed American	2.31%	43
Finnishnot grpmax-eligible	1.57%	64
Remaining individualsnot grpmax-eligible	0.514%	195
South Asian	0.353%	284
African / African-American	0.0889%	1,124
European (non-Finnish)	0.0646%	1,548
Middle Eastern	0.0503%	1,990

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.Gly707=
Coding: c.2121C>T
MANE Select: NM_214462
dbSNP: rs78695494
Type: single nucleotide variant
Location: chr6:168307636 (GRCh38)
Gene constraint: LOEUF 1.469 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.81
Residue 707: the 'disordered' region

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

Similar variants

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
DACT2 p.Ala332Thr 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-gly707 (accessed [today's date]).

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