NOVA2 p.Pro127=
c.381C>T · rs148155367 · VCV1298776
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0942%, 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 0.16 | GERP -5.6, phastCons 0.7 |
| Overall | ||
| CADD | 10.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0942%
European (non-Finnish) · 1,112/1,180,026 alleles
Filtering AF
0.0896%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0878%
Overall
0.075%
1,211/1,614,030 alleles · ultra-rare
exomes 1,157/1,461,852 · genomes 54/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0942% | 1,061 |
| Admixed American | 0.06% | 1,666 |
| Remaining individualsnot grpmax-eligible | 0.056% | 1,785 |
| South Asian | 0.0132% | 7,589 |
| African / African-American | 0.012% | 8,327 |
| Finnishnot grpmax-eligible | 0.00781% | 12,807 |
| East Asian | 0.00446% | 22,440 |
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.Pro127=
- Coding
- c.381C>T
- MANE Select
- NM_002516
- dbSNP
- rs148155367
- Type
- single nucleotide variant
- Location
- chr19:45953795 (GRCh38)
- Gene constraint
- LOEUF 0.611 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 65.60 · 2 PDB
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 c.-3C>A 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/nova2-p-pro127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown