CDSN p.Cys423Ser
c.1268G>C · VCV3350212
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0268%, amr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.159 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | phastCons 1 |
| Overall | ||
| CADD | 22.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0268%
Admixed American · 16/59,804 alleles
Filtering AF
0.0168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00105%
17/1,612,570 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0268% | 3,738 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,424 |
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.Cys423Ser
- Coding
- c.1268G>C
- MANE Select
- NM_001264
- Type
- single nucleotide variant
- Location
- chr6:31116347 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI 0.08 (gnomAD)
- Structure
- AlphaFold pLDDT 38.13
- Residue 423
- the 'disordered' region
Similar variants
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- CDSN p.Pro471Leu Uncertain significance ★★ same condition
- CDSN p.Ser159Gly Uncertain significance ★★ same condition
- CDSN p.Ser274Asn Uncertain significance ★★ same condition
- CDSN p.Val506Met Uncertain significance ★★ same condition
- CDSN p.Pro192Leu Likely benign ★★ same condition
- CDSN p.Ala368Gly Uncertain significance ★ same condition
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-cys423ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown