NRAP p.Ala446=
c.1338T>C · rs76861484 · VCV769788
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.15%, 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 -1.2 | GERP -4.6 |
| Overall | ||
| CADD | 1.334 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.15%
European (non-Finnish) · 13,411/1,162,888 alleles
Filtering AF
1.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.13%
Overall
0.94%
14,860/1,581,528 alleles · low-frequency
exomes 13,977/1,429,202 · genomes 883/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.15% | 87 |
| Remaining individualsnot grpmax-eligible | 1.06% | 95 |
| Middle Eastern | 0.873% | 115 |
| Amishnot grpmax-eligible | 0.768% | 130 |
| Admixed American | 0.365% | 274 |
| Ashkenazi Jewishnot grpmax-eligible | 0.359% | 279 |
| South Asian | 0.327% | 306 |
| African / African-American | 0.14% | 712 |
| Finnishnot grpmax-eligible | 0.0737% | 1,356 |
| East Asian | 0.00238% | 41,960 |
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
- NRAP
- Protein
- p.Ala446=
- Coding
- c.1338T>C
- MANE Select
- NM_198060
- dbSNP
- rs76861484
- Type
- single nucleotide variant
- Location
- chr10:113640317 (GRCh38)
- Gene constraint
- LOEUF 1.045 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.98
Similar variants
- NRAP p.Ala446Val Uncertain significance ★ ⚠ same residue
- NRAP p.Arg1037Ter Pathogenic/Likely pathogenic ★★ same type
- NRAP p.Trp1033Ter Pathogenic/Likely pathogenic ★★ same type
- NRAP c.360+1G>A Uncertain significance ★★ same type
- NRAP p.Ala29Gly Uncertain significance ★★ ⚠ same type
- NRAP p.Ala571Thr Uncertain significance ★★ same type
- NRAP p.Arg1330Gln Uncertain significance ★★ ⚠ same type
- NRAP p.Arg1559Gln 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/nrap-p-ala446 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown