CDSN p.Pro223=
c.669C>T · rs117764398 · VCV2051005
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.15%, eas)
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 -7.5 | |
| Overall | ||
| CADD | 0.194 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.15%
East Asian · 1,862/44,874 alleles
Filtering AF
3.99%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.93%
Overall
0.16%
2,589/1,614,168 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.15% | 24 |
| Middle Eastern | 0.116% | 866 |
| Ashkenazi Jewishnot grpmax-eligible | 0.105% | 955 |
| Remaining individualsnot grpmax-eligible | 0.0832% | 1,202 |
| Admixed American | 0.0583% | 1,715 |
| African / African-American | 0.048% | 2,084 |
| European (non-Finnish) | 0.0455% | 2,197 |
| South Asian | 0.0274% | 3,643 |
| Finnishnot grpmax-eligible | 0.00625% | 16,008 |
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
- CDSN
- Protein
- p.Pro223=
- Coding
- c.669C>T
- MANE Select
- NM_001264
- dbSNP
- rs117764398
- Type
- single nucleotide variant
- Location
- chr6:31116946 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI 0.08 (gnomAD)
- Structure
- AlphaFold pLDDT 38.13
- Residue 223
- the 'disordered' region
Similar variants
- CDSN p.Lys59Ter Pathogenic ★★ same type
- CDSN p.Cys423Ser Uncertain significance ★★ same type
- CDSN p.Gly335Ala Uncertain significance ★★ same type
- CDSN p.Pro226Ser Uncertain significance ★★ same type
- CDSN p.Pro282Thr Uncertain significance ★★ same type
- CDSN p.Pro447Leu Uncertain significance ★★ same type
- CDSN p.Pro471Leu Uncertain significance ★★ same type
- CDSN p.Ser159Gly 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/cdsn-p-pro223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown