RNF216 p.Pro919=
c.2757G>A · rs146694552 · VCV740477
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0955%, amr)
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 -15 | GERP -8.8 |
| Overall | ||
| CADD | 0.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0955%
Admixed American · 57/59,706 alleles
Filtering AF
0.0756%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0685%
Overall
0.0587%
941/1,602,110 alleles · ultra-rare
exomes 851/1,449,774 · genomes 90/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0955% | 1,047 |
| European (non-Finnish) | 0.0709% | 1,410 |
| Remaining individualsnot grpmax-eligible | 0.0404% | 2,478 |
| African / African-American | 0.0307% | 3,257 |
| Middle Eastern | 0.0166% | 6,022 |
| East Asian | 0.00449% | 22,279 |
| South Asian | 0.00221% | 45,256 |
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
- RNF216
- Protein
- p.Pro919=
- Coding
- c.2757G>A
- MANE Select
- NM_207111
- dbSNP
- rs146694552
- Type
- single nucleotide variant
- Location
- chr7:5622875 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.91 · 4 PDB
Similar variants
- RNF216 p.Pro919Leu Uncertain significance ★★ ⚠ same residue
- RNF216 p.Trp229Ter Pathogenic/Likely pathogenic ★★ same type
- RNF216 p.Ala314Pro Uncertain significance ★★ ⚠ same type
- RNF216 p.Ala588Thr Uncertain significance ★★ ⚠ same type
- RNF216 p.Ala652Val Uncertain significance ★★ ⚠ same type
- RNF216 p.Arg262His Uncertain significance ★★ ⚠ same type
- RNF216 p.Arg391Thr Uncertain significance ★★ ⚠ same type
- RNF216 p.Arg426His 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/rnf216-p-pro919 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown