RNF213 p.Ala1908=
c.5724G>A · rs757738943 · VCV1642956
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0185%, amr)
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 -9.5 | GERP -3.4 |
| Overall | ||
| CADD | 0.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0185%
Admixed American · 11/59,404 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00802%
Overall
0.00797%
128/1,606,968 alleles · ultra-rare
exomes 113/1,454,778 · genomes 15/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0185% | 5,400 |
| East Asian | 0.0157% | 6,367 |
| European (non-Finnish) | 0.00849% | 11,780 |
| Remaining individualsnot grpmax-eligible | 0.00642% | 15,572 |
| African / African-American | 0.00401% | 24,914 |
| South Asian | 0.00333% | 30,029 |
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.Ala1908=
- Coding
- c.5724G>A
- MANE Select
- NM_001256071
- dbSNP
- rs757738943
- Type
- single nucleotide variant
- Location
- chr17:80340091 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 (gnomAD)
- Residue 1908
- an α-helix
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-ala1908 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown