RNF216 p.Ala709=
c.2127T>C · VCV4774846
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, 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 0.65 | GERP -2.3, phastCons 0.94 |
| Overall | ||
| CADD | 7.192 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,926 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,613,676 alleles · very rare
exomes 1/1,461,500 · genomes 2/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,463 |
| European (non-Finnish) | 8.48e-05% | 1,179,727 |
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.Ala709=
- Coding
- c.2127T>C
- MANE Select
- NM_207111
- Type
- single nucleotide variant
- Location
- chr7:5652445 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.91 · 4 PDB
- Residue 709
- the 'triad supradomain' region; a β-strand
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-ala709 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown