CDSN p.Arg251=
c.753G>A · rs4713436 · VCV1237033
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 32.7%, sas) — too common for a highly-penetrant pathogenic allele
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 2.2 | phastCons 1 |
| Overall | ||
| CADD | 12.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
32.7%
South Asian · 29,765/91,062 alleles
Filtering AF
32.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 32.2%
Overall
17.8%
286,859/1,613,678 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 32.7% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 27% | 4 |
| Middle Eastern | 24.9% | 4 |
| East Asian | 19.9% | 5 |
| Admixed American | 19.8% | 5 |
| Finnishnot grpmax-eligible | 19.6% | 5 |
| Remaining individualsnot grpmax-eligible | 18.2% | 5 |
| European (non-Finnish) | 16.5% | 6 |
| African / African-American | 10.9% | 9 |
| Amishnot grpmax-eligible | 8% | 12 |
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.Arg251=
- Coding
- c.753G>A
- MANE Select
- NM_001264
- dbSNP
- rs4713436
- Type
- single nucleotide variant
- Location
- chr6:31116862 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI 0.08 (gnomAD)
- Structure
- AlphaFold pLDDT 38.13
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-arg251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown