RIN2 p.Thr843=
c.2529A>T · rs375395451 · VCV512337
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.108%, nfe)
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 -8.4 | GERP -10 |
| Overall | ||
| CADD | 0.048 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.108%
European (non-Finnish) · 1,278/1,179,898 alleles
Filtering AF
0.103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.101%
Overall
0.0888%
1,433/1,614,024 alleles · rare
exomes 1,350/1,461,710 · genomes 83/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.108% | 923 |
| Admixed American | 0.1% | 1,000 |
| Finnishnot grpmax-eligible | 0.0703% | 1,423 |
| Remaining individualsnot grpmax-eligible | 0.0656% | 1,524 |
| Middle Eastern | 0.0495% | 2,021 |
| African / African-American | 0.008% | 12,506 |
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.Thr843=
- Coding
- c.2529A>T
- MANE Select
- NM_018993
- dbSNP
- rs375395451
- Type
- single nucleotide variant
- Location
- chr20:20000777 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
- Residue 843
- the ras-associating domain
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-thr843 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown