RNF216 p.Phe269=
c.807C>T · rs1584549969 · VCV764553
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 0.16 | GERP -3.9, phastCons 0.73 |
| Overall | ||
| CADD | 0.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,874 alleles
Overall
0.000124%
2/1,614,106 alleles · very rare
exomes 2/1,461,880 · genomes 0/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,874 |
| European (non-Finnish) | 8.47e-05% | 1,180,018 |
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.Phe269=
- Coding
- c.807C>T
- MANE Select
- NM_207111
- dbSNP
- rs1584549969
- Type
- single nucleotide variant
- Location
- chr7:5741210 (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-phe269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown