CDSN p.Pro511Leu
c.1532C>T · rs754267246 · VCV2191245
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0522%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.208 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | phastCons 1 |
| Overall | ||
| CADD | 25.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0522%
Middle Eastern · 3/5,746 alleles
Filtering AF
0.0331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.00279%
45/1,611,846 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0522% | 1,915 |
| South Asian | 0.0439% | 2,275 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,544 |
| Admixed American | 0.00167% | 59,996 |
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.Pro511Leu
- Coding
- c.1532C>T
- MANE Select
- NM_001264
- dbSNP
- rs754267246
- Type
- single nucleotide variant
- Location
- chr6:31116083 (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-pro511leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown