Is DACT2 p.Lys495Glu (c.1483A>G) pathogenic?

DACT2 p.Lys495Glu (c.1483A>G) is classified Uncertain significance in DACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely benign (0.2644); Ultra-rare (popmax 0.0166%, mid).

How common is DACT2 p.Lys495Glu (c.1483A>G) in the general population?

DACT2 p.Lys495Glu (c.1483A>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about DACT2 p.Lys495Glu (c.1483A>G)?

AlphaMissense predicts likely benign (score 0.2644) — an in-silico prediction, not a clinical call.

DACT2 p.Lys495Glu

c.1483A>G · rs1291017988 · VCV2269834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2644 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2644	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -7.52	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 1.6	GERP -1.6, phastCons 0.011
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.68 · regional, not allelic
Overall
CADD	19.87	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,020 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00188%

Overall 0.00238% 37/1,552,094 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,020
European (non-Finnish)	0.00296%	33,739
South Asian	0.00238%	42,033

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.Lys495Glu
Coding: c.1483A>G
MANE Select: NM_214462
dbSNP: rs1291017988
Type: single nucleotide variant
Location: chr6:168308274 (GRCh38)
Gene constraint: LOEUF 1.469 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.81
Residue 495: the 'disordered' region

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

Similar variants

DACT2 p.Lys495Thr 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-lys495glu (accessed [today's date]).

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