NCSTN p.Pro353=
c.1059C>T · rs34884866 · VCV1167775
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.594%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.564 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -3.5 |
| Overall | ||
| CADD | 7.989 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.594%
African / African-American · 446/75,026 alleles
Filtering AF
0.549%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.531%
Overall
0.0366%
591/1,614,126 alleles · rare
exomes 334/1,461,874 · genomes 257/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.594% | 168 |
| Middle Eastern | 0.148% | 674 |
| Admixed American | 0.0583% | 1,715 |
| Remaining individualsnot grpmax-eligible | 0.056% | 1,786 |
| South Asian | 0.00659% | 15,180 |
| European (non-Finnish) | 0.005% | 20,000 |
| East Asian | 0.00223% | 44,880 |
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
- NCSTN
- Protein
- p.Pro353=
- Coding
- c.1059C>T
- MANE Select
- NM_015331
- dbSNP
- rs34884866
- Type
- single nucleotide variant
- Location
- chr1:160352949 (GRCh38)
- Gene constraint
- LOEUF 0.343 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.73 · 30 PDB
- Residue 353
- a β-strand
Similar variants
- NCSTN p.Ala207Pro Uncertain significance ★★ ⚠ same type
- NCSTN p.Ala298Thr Uncertain significance ★★ ⚠ same type
- NCSTN p.Ala484Thr Uncertain significance ★★ same type
- NCSTN p.Ala48Ser Uncertain significance ★★ ⚠ same type
- NCSTN p.Ala497Val Uncertain significance ★★ ⚠ same type
- NCSTN p.Ala664Gly Uncertain significance ★★ same type
- NCSTN p.Ala664Thr Uncertain significance ★★ same type
- NCSTN p.Arg105Trp 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/ncstn-p-pro353 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown