Is DKK2 p.Asp244Glu (c.732T>A) pathogenic?

DKK2 p.Asp244Glu (c.732T>A) is classified Uncertain significance in DKK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.5872); Absent from gnomAD v4.1.

How common is DKK2 p.Asp244Glu (c.732T>A) in the general population?

DKK2 p.Asp244Glu (c.732T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKK2 p.Asp244Glu (c.732T>A)?

AlphaMissense predicts likely pathogenic (score 0.5872) — an in-silico prediction, not a clinical call.

DKK2 p.Asp244Glu

c.732T>A · VCV4240890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5872	likely pathogenic
REVEL	0.241	benign-leaning
SaProt	LLR -4.30	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP -3.5, phastCons 0.71
Regional constraint	o/e 0.97	unconstrained · MANE · 112 kb · p 0.6 · regional, not allelic
Overall
CADD	17.15	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: DKK2
Protein: p.Asp244Glu
Coding: c.732T>A
MANE Select: NM_014421
Type: single nucleotide variant
Location: chr4:106924002 (GRCh38)
Gene constraint: LOEUF 0.621 · pLI 0.61 (gnomAD)
Structure: AlphaFold pLDDT 70.82
Residue 244: the 'dkk-type cys-2' region; a disulfide bond

Full DKK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DKK2 p.Ala3Thr Uncertain significance ★ ⚠ same type
DKK2 p.Ala75Thr Uncertain significance ★ ⚠ same type
DKK2 p.Arg104Gln Uncertain significance ★ ⚠ same type
DKK2 p.Arg218Cys Uncertain significance ★ ⚠ same type
DKK2 p.Asn36Lys Uncertain significance ★ ⚠ same type
DKK2 p.Asp232Asn Uncertain significance ★ ⚠ same type
DKK2 p.Asp9Tyr Uncertain significance ★ ⚠ same type
DKK2 p.Cys189Ser 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/dkk2-p-asp244glu (accessed [today's date]).

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