Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele
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 -2.9 | GERP -4 |
| Overall | ||
| CADD | 5.951 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.2%
African / African-American · 7,638/74,970 alleles
Filtering AF
10%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.92%
Overall
0.567%
9,153/1,613,908 alleles · common
exomes 4,872/1,461,750 · genomes 4,281/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.2% | 10 |
| Remaining individualsnot grpmax-eligible | 0.781% | 128 |
| Middle Eastern | 0.775% | 129 |
| Admixed American | 0.64% | 156 |
| European (non-Finnish) | 0.0471% | 2,122 |
| South Asian | 0.0351% | 2,846 |
| Ashkenazi Jewishnot grpmax-eligible | 0.027% | 3,699 |
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
- NRIP1
- Protein
- p.Pro951=
- Coding
- c.2853G>A
- MANE Select
- NM_003489
- dbSNP
- rs2228508
- Type
- single nucleotide variant
- Location
- chr21:14965340 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 46.10 · 17 PDB
- Residue 951
- the 'interaction with znf366' region; the 'disordered' region
Similar variants
- NRIP1 p.Pro951Leu Uncertain significance ★★ ⚠ same residue
- NRIP1 p.Ala1096Gly Uncertain significance ★★ ⚠ same type
- NRIP1 p.Ala360Ser Uncertain significance ★★ ⚠ same type
- NRIP1 p.Ala36Pro Uncertain significance ★★ ⚠ same type
- NRIP1 p.Ala792Val Uncertain significance ★★ ⚠ same type
- NRIP1 p.Arg1082Gly Uncertain significance ★★ ⚠ same type
- NRIP1 p.Arg1122Gly Uncertain significance ★★ ⚠ same type
- NRIP1 p.Arg98Trp 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/nrip1-p-pro951 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown