RNF216 p.Pro663=
c.1989G>A · VCV4895154
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.029%, 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 1.1 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 14.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.029%
East Asian · 13/44,894 alleles
Filtering AF
0.0171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00304%
49/1,613,638 alleles · ultra-rare
exomes 41/1,461,450 · genomes 8/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.029% | 3,453 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,412 |
| African / African-American | 0.00667% | 14,986 |
| Admixed American | 0.005% | 19,984 |
| South Asian | 0.0033% | 30,324 |
| European (non-Finnish) | 0.00161% | 62,096 |
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.Pro663=
- Coding
- c.1989G>A
- MANE Select
- NM_207111
- Type
- single nucleotide variant
- Location
- chr7:5711833 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.91 · 4 PDB
- Residue 663
- the 'triad supradomain' region; an α-helix
Similar variants
- RNF216 p.Pro663Leu 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-pro663 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown