Is DKK1 p.Arg224= (c.672G>A) pathogenic?

DKK1 p.Arg224= (c.672G>A) is classified Likely benign in DKK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-04). Ultra-rare (popmax 0.0267%, amr).

How common is DKK1 p.Arg224= (c.672G>A) in the general population?

DKK1 p.Arg224= (c.672G>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

DKK1 p.Arg224=

c.672G>A · rs200588937 · VCV738698

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

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 1.3	GERP 0.33, phastCons 0.99
Overall
CADD	6.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,024 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00266% 43/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,752
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.00203%	49,167
African / African-American	0.00133%	75,038

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: DKK1
Protein: p.Arg224=
Coding: c.672G>A
MANE Select: NM_012242
dbSNP: rs200588937
Type: single nucleotide variant
Location: chr10:52316678 (GRCh38)
Gene constraint: LOEUF 1.101 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.68 · 5 PDB
Residue 224: a disulfide bond; the 'dkk-type cys-2' region

Full DKK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DKK1 c.244-6C>T Benign ★★ same type
DKK1 c.548-4G>A Benign/Likely benign ★★ same type
DKK1 p.Ala113Thr Conflicting classifications of pathogenicity ★ ⚠ same type
DKK1 p.Ala196Val Uncertain significance ★ ⚠ same type
DKK1 p.Ala19Thr Uncertain significance ★ ⚠ same type
DKK1 p.Ala98Pro Uncertain significance ★ ⚠ same type
DKK1 p.Arg115Lys Uncertain significance ★ ⚠ same type
DKK1 p.Arg11Gln 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/dkk1-p-arg224 (accessed [today's date]).

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