NCDN p.Pro533=
c.1599G>A · rs1140731 · VCV2638650
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.218 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -3.5 |
| Overall | ||
| CADD | 4.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/59,996 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00785%
Overall
0.00161%
26/1,613,456 alleles · ultra-rare
exomes 22/1,461,236 · genomes 4/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,454 |
| East Asian | 0.0134% | 7,478 |
| African / African-American | 0.00267% | 37,462 |
| South Asian | 0.0011% | 91,078 |
| European (non-Finnish) | 0.000509% | 196,595 |
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
- NCDN
- Protein
- p.Pro533=
- Coding
- c.1599G>A
- MANE Select
- NM_014284
- dbSNP
- rs1140731
- Type
- single nucleotide variant
- Location
- chr1:35563415 (GRCh38)
- Gene constraint
- LOEUF 0.261 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 88.12
Similar variants
- NCDN p.Pro533Leu Likely pathogenic ★ same residue
- NCDN p.Pro533Arg Uncertain significance ★ ⚠ same residue
- NCDN p.Arg259Trp Uncertain significance ★★ ⚠ same type
- NCDN p.Arg423His Uncertain significance ★★ ⚠ same type
- NCDN p.Gly164Ser Uncertain significance ★★ ⚠ same type
- NCDN p.Gly189Ser Uncertain significance ★★ ⚠ same type
- NCDN p.Arg478Gln Pathogenic ★ ⚠ same type
- NCDN p.Glu433Gln Likely pathogenic ★ ⚠ 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/ncdn-p-pro533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown