NOVA2 p.Glu4=
c.12G>A · rs777493618 · VCV1879446
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00465%, 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 3.1 | GERP 0.33, phastCons 1 |
| Overall | ||
| CADD | 9.803 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00465%
European (non-Finnish) · 46/990,084 alleles
Filtering AF
0.00356%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00319%
Overall
0.00399%
50/1,252,450 alleles · very rare
exomes 45/1,106,412 · genomes 5/146,038 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00465% | 21,524 |
| Remaining individualsnot grpmax-eligible | 0.00434% | 23,031 |
| Finnishnot grpmax-eligible | 0.00268% | 37,326 |
| African / African-American | 0.00158% | 63,354 |
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.Glu4=
- Coding
- c.12G>A
- MANE Select
- NM_002516
- dbSNP
- rs777493618
- Type
- single nucleotide variant
- Location
- chr19:45973340 (GRCh38)
- Gene constraint
- LOEUF 0.611 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 65.60 · 2 PDB
Similar variants
- NOVA2 p.Glu4Lys Uncertain significance ★ ⚠ same residue
- 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
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-glu4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown