Is DKK2 p.Asp232Asn (c.694G>A) pathogenic?

DKK2 p.Asp232Asn (c.694G>A) is classified Uncertain significance in DKK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: ambiguous (0.3755); Very rare (popmax 0.00333%, amr).

How common is DKK2 p.Asp232Asn (c.694G>A) in the general population?

DKK2 p.Asp232Asn (c.694G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DKK2 p.Asp232Asn (c.694G>A)?

AlphaMissense predicts ambiguous (score 0.3755) — an in-silico prediction, not a clinical call.

DKK2 p.Asp232Asn

c.694G>A · rs768079972 · VCV2398988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3755 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3755	ambiguous
REVEL	0.211	benign-leaning
SaProt	LLR -7.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 112 kb · p 0.6 · regional, not allelic
Overall
CADD	26.3	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 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000958% 14/1,461,754 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
African / African-American	0.00267%	37,488
East Asian	0.00223%	44,858
South Asian	0.0022%	45,530
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.000509%	196,656

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: DKK2
Protein: p.Asp232Asn
Coding: c.694G>A
MANE Select: NM_014421
dbSNP: rs768079972
Type: single nucleotide variant
Location: chr4:106924040 (GRCh38)
Gene constraint: LOEUF 0.621 · pLI 0.61 (gnomAD)
Structure: AlphaFold pLDDT 70.82
Residue 232: 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.Asp244Glu 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-asp232asn (accessed [today's date]).

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