RNF213 p.Leu725=
c.2175C>T · VCV3668439
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.57%, eas)
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 0.38 | GERP 0.33, phastCons 0.036 |
| Overall | ||
| CADD | 4.839 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.57%
East Asian · 256/44,892 alleles
Filtering AF
0.513%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.491%
Overall
0.0175%
283/1,614,226 alleles · rare
exomes 231/1,461,888 · genomes 52/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.57% | 175 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| Admixed American | 0.005% | 20,006 |
| South Asian | 0.0022% | 45,542 |
| European (non-Finnish) | 0.000339% | 295,014 |
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.Leu725=
- Coding
- c.2175C>T
- MANE Select
- NM_001256071
- Type
- single nucleotide variant
- Location
- chr17:80298483 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 (gnomAD)
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-leu725 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown