RNF216 p.Arg751=
c.2253C>T · rs150148326 · VCV1562652
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.119%, 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 4.4 | GERP 6.7, phastCons 1 |
| Overall | ||
| CADD | 11.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.119%
African / African-American · 89/75,028 alleles
Filtering AF
0.0987%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0913%
Overall
0.00595%
96/1,614,150 alleles · rare
exomes 46/1,461,884 · genomes 50/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.119% | 843 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,837 |
| European (non-Finnish) | 0.000339% | 295,007 |
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.Arg751=
- Coding
- c.2253C>T
- MANE Select
- NM_207111
- dbSNP
- rs150148326
- Type
- single nucleotide variant
- Location
- chr7:5641283 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.91 · 4 PDB
- Residue 751
- an α-helix
Similar variants
- RNF216 p.Arg751Cys Likely pathogenic ★ same residue
- RNF216 p.Arg751His 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
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-arg751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown