NRIP1 p.Pro233=
c.699G>C · rs190171837 · VCV2732283
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0987%, mid)
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 0.1 | GERP -1.7, phastCons 0.001 |
| Overall | ||
| CADD | 1.131 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0987%
Middle Eastern · 6/6,082 alleles
Filtering AF
0.0429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.00818%
132/1,613,978 alleles · ultra-rare
exomes 121/1,461,842 · genomes 11/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0987% | 1,014 |
| South Asian | 0.0296% | 3,373 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,676 |
| African / African-American | 0.00668% | 14,981 |
| Admixed American | 0.00667% | 14,997 |
| European (non-Finnish) | 0.0061% | 16,389 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
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.Pro233=
- Coding
- c.699G>C
- MANE Select
- NM_003489
- dbSNP
- rs190171837
- Type
- single nucleotide variant
- Location
- chr21:14967494 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 46.10 · 17 PDB
- Residue 233
- the 'interaction with znf366' region; the 'repression domain 1' region
Similar variants
- NRIP1 p.Pro233Arg 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-pro233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown