RIN2 p.Pro475=
c.1425C>A · rs188147644 · VCV212053
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.44%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.26 | GERP -2.9, phastCons 0.22 |
| Overall | ||
| CADD | 6.372 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.44%
Middle Eastern · 87/6,062 alleles
Filtering AF
1.19%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1%
Overall
0.506%
8,161/1,614,044 alleles · low-frequency
exomes 7,561/1,461,710 · genomes 600/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.44% | 70 |
| Ashkenazi Jewishnot grpmax-eligible | 0.763% | 131 |
| European (non-Finnish) | 0.581% | 172 |
| Remaining individualsnot grpmax-eligible | 0.535% | 187 |
| Admixed American | 0.513% | 195 |
| South Asian | 0.274% | 364 |
| African / African-American | 0.123% | 816 |
| Finnishnot grpmax-eligible | 0.0141% | 7,114 |
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
- RIN2
- Protein
- p.Pro475=
- Coding
- c.1425C>A
- MANE Select
- NM_018993
- dbSNP
- rs188147644
- Type
- single nucleotide variant
- Location
- chr20:19975450 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
- Residue 475
- the 'disordered' region
Similar variants
- RIN2 p.Ala205Val Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala72Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala8Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg135Cys Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg170Trp Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg255Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg290Leu Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg303Gln 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/rin2-p-pro475 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown