RIN1 p.Ala690=
c.2070C>T · rs145710377 · VCV776629
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.64%, afr)
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 2.4 | GERP -2.7, phastCons 1 |
| Overall | ||
| CADD | 8.042 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.64%
African / African-American · 2,731/75,016 alleles
Filtering AF
3.53%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.48%
Overall
0.197%
3,184/1,612,924 alleles · low-frequency
exomes 1,677/1,460,602 · genomes 1,507/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.64% | 27 |
| Remaining individualsnot grpmax-eligible | 0.303% | 330 |
| Middle Eastern | 0.248% | 404 |
| Admixed American | 0.233% | 428 |
| South Asian | 0.0176% | 5,690 |
| European (non-Finnish) | 0.00789% | 12,680 |
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
- RIN1
- Protein
- p.Ala690=
- Coding
- c.2070C>T
- MANE Select
- NM_004292
- dbSNP
- rs145710377
- Type
- single nucleotide variant
- Location
- chr11:66332558 (GRCh38)
- Gene constraint
- LOEUF 1.22 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.78
- Residue 690
- the ras-associating domain; the 'ras and 14-3-3 protein binding region' region
Similar variants
- RIN1 p.Gly737= Benign ★★ same type
- RIN1 p.Thr643= Benign/Likely benign ★★ same type
- RIN1 p.Val700Ile Benign ★★ same type
- RIN1 p.Ala111Thr Uncertain significance ★ ⚠ same type
- RIN1 p.Ala168Thr Uncertain significance ★ ⚠ same type
- RIN1 p.Ala221Ser Uncertain significance ★ ⚠ same type
- RIN1 p.Ala31Val Uncertain significance ★ ⚠ same type
- RIN1 p.Ala368Val 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/rin1-p-ala690 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown