NOVA2 p.Thr466=
c.1398G>A · VCV3905712
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, 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 0.18 | GERP -3.7, phastCons 0.97 |
| Overall | ||
| CADD | 10.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,179,960 alleles
Overall
6.2e-05%
1/1,614,018 alleles · very rare
exomes 1/1,461,764 · genomes 0/152,254 · joint denominator
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
- NOVA2
- Protein
- p.Thr466=
- Coding
- c.1398G>A
- MANE Select
- NM_002516
- Type
- single nucleotide variant
- Location
- chr19:45939944 (GRCh38)
- Gene constraint
- LOEUF 0.611 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 65.60 · 2 PDB
- Residue 466
- an α-helix; the kh 3 domain
Similar variants
- NOVA2 p.Ala247Thr Uncertain significance ★★ ⚠ same type
- NOVA2 p.Ala287= Benign ★★ same type
- NOVA2 p.Ala383= Benign/Likely benign ★★ same type
- NOVA2 p.Asn292Thr Likely benign ★★ same type
- NOVA2 p.Ile39= Benign/Likely benign ★★ same type
- NOVA2 p.Leu135= Likely benign ★★ same type
- NOVA2 p.Leu238= Benign ★★ same type
- NOVA2 p.Pro127= Likely benign ★★ 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/nova2-p-thr466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown