NRAP p.Ser490=
c.1470G>A · rs142887772 · VCV783581
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.77%, afr)
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 -0.61 | GERP -4.2 |
| Overall | ||
| CADD | 2.337 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.77%
African / African-American · 1,330/75,016 alleles
Filtering AF
1.69%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.66%
Overall
0.112%
1,810/1,613,890 alleles · low-frequency
exomes 1,019/1,461,678 · genomes 791/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.77% | 56 |
| Remaining individualsnot grpmax-eligible | 0.213% | 470 |
| Admixed American | 0.183% | 546 |
| Middle Eastern | 0.165% | 606 |
| Ashkenazi Jewishnot grpmax-eligible | 0.115% | 871 |
| South Asian | 0.0681% | 1,469 |
| European (non-Finnish) | 0.0111% | 9,006 |
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.Ser490=
- Coding
- c.1470G>A
- MANE Select
- NM_198060
- dbSNP
- rs142887772
- Type
- single nucleotide variant
- Location
- chr10:113634169 (GRCh38)
- Gene constraint
- LOEUF 1.045 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.98
- Residue 490
- a UniProt-annotated variant site (in)
Similar variants
- NRAP p.Ser490Leu Benign ★★ 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-ser490 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown