CDSN p.Arg500Trp
c.1498C>T · rs138408228 · VCV1978884
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.305 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.8 | phastCons 1 |
| Overall | ||
| CADD | 27.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,040 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000807%
13/1,610,904 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,040 |
| African / African-American | 0.00401% | 24,957 |
| South Asian | 0.0011% | 90,984 |
| European (non-Finnish) | 0.000679% | 147,313 |
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.Arg500Trp
- Coding
- c.1498C>T
- MANE Select
- NM_001264
- dbSNP
- rs138408228
- Type
- single nucleotide variant
- Location
- chr6:31116117 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI 0.08 (gnomAD)
- Structure
- AlphaFold pLDDT 38.13
Similar variants
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- 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
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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-arg500trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown