RIN2 p.Pro308=
c.924A>C · rs1348842250 · VCV695293
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 11%, nfe) — too common for a highly-penetrant pathogenic allele
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 0.26 | GERP -4.4, phastCons 0.49 |
| Overall | ||
| CADD | 7.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11%
European (non-Finnish) · 38,680/350,366 alleles
Filtering AF
10.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.9%
Overall
8.54%
44,626/522,258 alleles · common
exomes 43,526/443,732 · genomes 1,100/78,526 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 11% | 9 |
| Remaining individualsnot grpmax-eligible | 8.62% | 12 |
| Ashkenazi Jewishnot grpmax-eligible | 4.53% | 22 |
| Admixed American | 3.8% | 26 |
| African / African-American | 3.48% | 29 |
| Middle Eastern | 3.27% | 31 |
| South Asian | 3.01% | 33 |
| East Asian | 1.74% | 58 |
| Amishnot grpmax-eligible | 1.55% | 64 |
| Finnishnot grpmax-eligible | 0.958% | 104 |
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.Pro308=
- Coding
- c.924A>C
- MANE Select
- NM_018993
- dbSNP
- rs1348842250
- Type
- single nucleotide variant
- Location
- chr20:19974949 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
- Residue 308
- the 'disordered' region
Similar variants
- RIN2 p.Pro308Ala Uncertain significance ★★ ⚠ same residue
- RIN2 p.Pro308Arg Uncertain significance ★★ ⚠ same residue
- RIN2 p.Pro308Gln Uncertain significance ★★ ⚠ same residue
- RIN2 p.Pro308Leu Uncertain significance ★★ ⚠ same residue
- RIN2 p.Pro308fs Pathogenic ★ same residue
- RIN2 p.Ala205Val Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala72Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala8Thr 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-pro308 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown