NOVA2 p.Thr141=
c.423G>A · rs368021609 · VCV2571049
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -5.2 |
| Overall | ||
| CADD | 4.064 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00568%
European (non-Finnish) · 67/1,179,738 alleles
Filtering AF
0.00454%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00417%
Overall
0.00449%
72/1,604,264 alleles · very rare
exomes 65/1,452,084 · genomes 7/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00568% | 17,608 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,803 |
| East Asian | 0.00223% | 44,844 |
| African / African-American | 0.00133% | 74,910 |
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.Thr141=
- Coding
- c.423G>A
- MANE Select
- NM_002516
- dbSNP
- rs368021609
- Type
- single nucleotide variant
- Location
- chr19:45940919 (GRCh38)
- Gene constraint
- LOEUF 0.611 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 65.60 · 2 PDB
- Residue 141
- the kh 2 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-thr141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown