RNF216 p.Pro827=
c.2481G>A · rs146356109 · VCV2081561
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.154%, 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 -1.2 | GERP -4.1 |
| Overall | ||
| CADD | 2.636 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.154%
African / African-American · 115/74,478 alleles
Filtering AF
0.132%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.00823%
130/1,579,508 alleles · rare
exomes 59/1,427,236 · genomes 71/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.154% | 648 |
| Admixed American | 0.00687% | 14,548 |
| East Asian | 0.00226% | 44,278 |
| Remaining individualsnot grpmax-eligible | 0.00164% | 60,964 |
| South Asian | 0.00115% | 87,020 |
| European (non-Finnish) | 0.000691% | 144,645 |
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.Pro827=
- Coding
- c.2481G>A
- MANE Select
- NM_207111
- dbSNP
- rs146356109
- Type
- single nucleotide variant
- Location
- chr7:5623151 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.91 · 4 PDB
Similar variants
- RNF216 p.Pro827Leu 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-pro827 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown