NSUN2 p.Pro187=
c.561T>C · rs186098993 · VCV436086
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.036%, afr)
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 -3.1 | GERP -1.1 |
| Overall | ||
| CADD | 6.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.036%
African / African-American · 27/75,078 alleles
Filtering AF
0.0253%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0218%
Overall
0.00198%
32/1,614,086 alleles · ultra-rare
exomes 17/1,461,688 · genomes 15/152,398 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.036% | 2,781 |
| Admixed American | 0.00833% | 12,007 |
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
- NSUN2
- Protein
- p.Pro187=
- Coding
- c.561T>C
- MANE Select
- NM_017755
- dbSNP
- rs186098993
- Type
- single nucleotide variant
- Location
- chr5:6622077 (GRCh38)
- Gene constraint
- LOEUF 0.965 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.09 · 11 PDB
- Residue 187
- a binding site
Similar variants
- NSUN2 p.Pro187fs Pathogenic ★ same residue
- NSUN2 c.1601+1G>A Likely pathogenic ★★ same type
- NSUN2 c.360-1G>C Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Arg264Ter Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Arg389Ter Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Arg408Ter Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Ser139Ter Pathogenic ★★ same type
- NSUN2 p.Trp377Ter 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/nsun2-p-pro187 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown