NCSTN p.Ser641=
c.1923C>T · rs200925288 · VCV2961134
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00568%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 11.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00568%
European (non-Finnish) · 67/1,180,020 alleles
Filtering AF
0.00453%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00417%
Overall
0.00421%
68/1,614,022 alleles · very rare
exomes 65/1,461,884 · genomes 3/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00568% | 17,612 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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.Ser641=
- Coding
- c.1923C>T
- MANE Select
- NM_015331
- dbSNP
- rs200925288
- Type
- single nucleotide variant
- Location
- chr1:160357169 (GRCh38)
- Gene constraint
- LOEUF 0.343 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.73 · 30 PDB
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-ser641 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown