RIN2 p.Ser418=
c.1254A>G · rs367600361 · VCV2076399
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.021%, 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 1.4 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 7.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.021%
Admixed American · 12/57,152 alleles
Filtering AF
0.0121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0095%
Overall
0.00476%
76/1,596,354 alleles · ultra-rare
exomes 67/1,444,176 · genomes 9/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.021% | 4,763 |
| Remaining individualsnot grpmax-eligible | 0.0146% | 6,868 |
| Finnishnot grpmax-eligible | 0.0097% | 10,307 |
| European (non-Finnish) | 0.00401% | 24,933 |
| African / African-American | 0.00268% | 37,313 |
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.Ser418=
- Coding
- c.1254A>G
- MANE Select
- NM_018993
- dbSNP
- rs367600361
- Type
- single nucleotide variant
- Location
- chr20:19975279 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
- Residue 418
- 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-ser418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown