RIPK1 p.Pro361=
c.1083T>C · rs114175266 · VCV1667136
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.655%, 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 -3.5 | GERP -4.5 |
| Overall | ||
| CADD | 2.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.655%
African / African-American · 491/75,016 alleles
Filtering AF
0.607%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.588%
Overall
0.0333%
537/1,612,040 alleles · rare
exomes 278/1,459,732 · genomes 259/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.655% | 153 |
| Admixed American | 0.0334% | 2,994 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,467 |
| Middle Eastern | 0.0165% | 6,048 |
| European (non-Finnish) | 0.000594% | 168,401 |
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
- RIPK1
- Protein
- p.Pro361=
- Coding
- c.1083T>C
- MANE Select
- NM_001354930
- dbSNP
- rs114175266
- Type
- single nucleotide variant
- Location
- chr6:3105558 (GRCh38)
- Gene constraint
- LOEUF 0.6 · pLI 0.21 (gnomAD)
- Structure
- AlphaFold pLDDT 70.38 · 39 PDB
- Residue 361
- the 'interaction with sqstm1' region
Similar variants
- RIPK1 p.Pro361Leu Uncertain significance ★ ⚠ same residue
- RIPK1 p.Asp324Asn Pathogenic ★★ ⚠ same type
- RIPK1 p.Asp324His Pathogenic ★★ ⚠ same type
- RIPK1 c.460-5C>A Uncertain significance ★★ same type
- RIPK1 p.Ala106Val Uncertain significance ★★ ⚠ same type
- RIPK1 p.Ala160Thr Uncertain significance ★★ ⚠ same type
- RIPK1 p.Ala194Thr Uncertain significance ★★ ⚠ same type
- RIPK1 p.Ala203Thr 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/ripk1-p-pro361 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown