NSUN2 p.Ser322=
c.966A>G · VCV4705412
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -5 |
| Overall | ||
| CADD | 0.083 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
Middle Eastern · 1/5,952 alleles
Filtering AF
0.00055%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000435%
Overall
0.000888%
14/1,576,150 alleles · ultra-rare
exomes 14/1,459,358 · genomes 0/116,792 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0168% | 5,952 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,806 |
| European (non-Finnish) | 0.00103% | 96,926 |
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.Ser322=
- Coding
- c.966A>G
- MANE Select
- NM_017755
- Type
- single nucleotide variant
- Location
- chr5:6616782 (GRCh38)
- Gene constraint
- LOEUF 0.965 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.09 · 11 PDB
Similar variants
- 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
- NSUN2 c.1226+4A>T 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/nsun2-p-ser322 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown