RIPK1 p.Pro272=
c.816G>A · rs114145894 · VCV1655900
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
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 -2.7 | GERP -5 |
| Overall | ||
| CADD | 0.551 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,018 alleles
Filtering AF
0.00334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00302%
Overall
0.00366%
59/1,614,166 alleles · very rare
exomes 56/1,461,862 · genomes 3/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,004 |
| European (non-Finnish) | 0.00432% | 23,138 |
| East Asian | 0.00223% | 44,886 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| African / African-American | 0.00133% | 75,038 |
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.Pro272=
- Coding
- c.816G>A
- MANE Select
- NM_001354930
- dbSNP
- rs114145894
- Type
- single nucleotide variant
- Location
- chr6:3085386 (GRCh38)
- Gene constraint
- LOEUF 0.6 · pLI 0.21 (gnomAD)
- Structure
- AlphaFold pLDDT 70.38 · 39 PDB
- Residue 272
- the protein kinase domain; an α-helix
Similar variants
- RIPK1 p.Pro272Leu 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-pro272 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown