RNF213 p.Pro3996=
c.11988G>A · rs77506504 · VCV1549558
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 14.8%, eas) — too common for a highly-penetrant pathogenic allele
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 -14 | GERP -3.2 |
| Overall | ||
| CADD | 0.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
14.8%
East Asian · 6,655/44,874 alleles
Filtering AF
14.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 14.4%
Overall
0.754%
12,166/1,614,192 alleles · common
exomes 10,724/1,461,888 · genomes 1,442/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 14.8% | 7 |
| Admixed American | 5.09% | 20 |
| Remaining individualsnot grpmax-eligible | 0.904% | 111 |
| Finnishnot grpmax-eligible | 0.689% | 145 |
| South Asian | 0.506% | 198 |
| Ashkenazi Jewishnot grpmax-eligible | 0.287% | 348 |
| African / African-American | 0.16% | 625 |
| Middle Eastern | 0.099% | 1,010 |
| European (non-Finnish) | 0.0661% | 1,513 |
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.Pro3996=
- Coding
- c.11988G>A
- MANE Select
- NM_001256071
- dbSNP
- rs77506504
- Type
- single nucleotide variant
- Location
- chr17:80367976 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 (gnomAD)
- Residue 3996
- a UniProt-annotated variant site (rare variant detected in cases of moyamoya disease)
Similar variants
- RNF213 p.Pro3996Leu Uncertain significance ★★ ⚠ same residue
- RNF213 p.Pro3996_Cys3997delinsGlyLeuGly Pathogenic ★ 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
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-pro3996 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown