RNF216 p.Pro846=
c.2538G>A · rs142956703 · VCV788419
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.93%, 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 -12 | GERP -14 |
| Overall | ||
| CADD | 0.038 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.93%
African / African-American · 697/74,966 alleles
Filtering AF
0.873%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.85%
Overall
0.0546%
879/1,610,566 alleles · rare
exomes 471/1,458,304 · genomes 408/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.93% | 108 |
| Remaining individualsnot grpmax-eligible | 0.077% | 1,299 |
| Admixed American | 0.0701% | 1,426 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0169% | 5,908 |
| South Asian | 0.0121% | 8,264 |
| East Asian | 0.0067% | 14,917 |
| European (non-Finnish) | 0.0062% | 16,127 |
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.Pro846=
- Coding
- c.2538G>A
- MANE Select
- NM_207111
- dbSNP
- rs142956703
- Type
- single nucleotide variant
- Location
- chr7:5623094 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.91 · 4 PDB
Similar variants
- RNF216 p.Pro846Leu 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-pro846 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown