RNF213 p.Pro194=
c.582G>A · VCV4684261
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0895%, afr)
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 -8.9 | GERP -2.5 |
| Overall | ||
| CADD | 1.292 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0895%
African / African-American · 67/74,880 alleles
Filtering AF
0.0722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.066%
Overall
0.0203%
326/1,609,396 alleles · ultra-rare
exomes 287/1,457,192 · genomes 39/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0895% | 1,118 |
| South Asian | 0.056% | 1,784 |
| European (non-Finnish) | 0.0165% | 6,068 |
| Remaining individualsnot grpmax-eligible | 0.0145% | 6,915 |
| Admixed American | 0.00668% | 14,973 |
| Finnishnot grpmax-eligible | 0.00159% | 63,052 |
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
- RNF213
- Protein
- p.Pro194=
- Coding
- c.582G>A
- MANE Select
- NM_001256071
- Type
- single nucleotide variant
- Location
- chr17:80288135 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 (gnomAD)
- Residue 194
- the 'disordered' region
Similar variants
- RNF213 p.Ala5114Thr Uncertain significance ★★ ⚠ same type
- RNF213 p.Arg2727Gly Uncertain significance ★★ ⚠ same type
- RNF213 p.Arg3585His Uncertain significance ★★ ⚠ same type
- RNF213 p.Arg4276Trp Uncertain significance ★★ ⚠ same type
- RNF213 p.Arg4492Gln Uncertain significance ★★ ⚠ same type
- RNF213 p.Arg4810Ser Uncertain significance ★★ ⚠ same type
- RNF213 p.Arg4958Trp Uncertain significance ★★ ⚠ same type
- RNF213 p.Asn1439Ser 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/rnf213-p-pro194 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown