RNF31 p.Ala28=
c.84G>A · rs749786038 · VCV2986779
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0108%, 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 -2.1 | GERP -5.2 |
| Overall | ||
| CADD | 7.739 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0108%
Admixed American · 6/55,688 alleles
Filtering AF
0.00466%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00313%
Overall
0.000441%
7/1,585,876 alleles · ultra-rare
exomes 7/1,433,536 · genomes 0/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0108% | 9,281 |
| European (non-Finnish) | 8.56e-05% | 1,168,835 |
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
- RNF31
- Protein
- p.Ala28=
- Coding
- c.84G>A
- MANE Select
- NM_017999
- dbSNP
- rs749786038
- Type
- single nucleotide variant
- Location
- chr14:24147782 (GRCh38)
- Gene constraint
- LOEUF 0.37 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.39 · 36 PDB
- Residue 28
- an α-helix; the 'polyubiquitin-binding' region
Similar variants
- RNF31 p.Ala28Thr Uncertain significance ★ ⚠ same residue
- RNF31 p.Ala251Val Uncertain significance ★★ ⚠ same type
- RNF31 p.Ala350Gly Uncertain significance ★★ ⚠ same type
- RNF31 p.Ala45Val Uncertain significance ★★ ⚠ same type
- RNF31 p.Ala501Thr Uncertain significance ★★ ⚠ same type
- RNF31 p.Ala503Ser Uncertain significance ★★ ⚠ same type
- RNF31 p.Ala503Thr Uncertain significance ★★ ⚠ same type
- RNF31 p.Ala539Val 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/rnf31-p-ala28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown