RNF213 p.Pro253=
c.759C>T · VCV3605295
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -0.92 | GERP -2.5 |
| Overall | ||
| CADD | 8.361 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000868%
14/1,612,766 alleles · ultra-rare
exomes 13/1,460,654 · genomes 1/152,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| East Asian | 0.00446% | 22,437 |
| Admixed American | 0.00333% | 29,996 |
| South Asian | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000678% | 147,496 |
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.Pro253=
- Coding
- c.759C>T
- MANE Select
- NM_001256071
- Type
- single nucleotide variant
- Location
- chr17:80288312 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 (gnomAD)
- Residue 253
- the 'disordered' region
Similar variants
- RNF213 p.Pro253Ser Likely benign ★★ same residue
- 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
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-pro253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown