RNF216 p.Pro272=
c.816C>T · rs75148631 · VCV778295
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -1.1 |
| Overall | ||
| CADD | 3.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.11%
African / African-American · 3,835/75,004 alleles
Filtering AF
4.98%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.92%
Overall
0.277%
4,465/1,614,076 alleles · common
exomes 2,184/1,461,872 · genomes 2,281/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.11% | 20 |
| Admixed American | 0.413% | 242 |
| Remaining individualsnot grpmax-eligible | 0.349% | 287 |
| Middle Eastern | 0.281% | 356 |
| European (non-Finnish) | 0.0119% | 8,429 |
| South Asian | 0.00549% | 18,216 |
| Finnishnot grpmax-eligible | 0.00312% | 32,011 |
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.Pro272=
- Coding
- c.816C>T
- MANE Select
- NM_207111
- dbSNP
- rs75148631
- Type
- single nucleotide variant
- Location
- chr7:5741201 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.91 · 4 PDB
Similar variants
- 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
- RNF216 p.Arg525Gln 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-pro272 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown