RIPK1 p.Ser296=
c.888T>C · rs113602774 · VCV1585399
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0914%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor gain, 27 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.4 | GERP -4.2 |
| Overall | ||
| CADD | 8.478 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0914%
African / African-American · 68/74,372 alleles
Filtering AF
0.0739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0676%
Overall
0.00535%
85/1,587,568 alleles · ultra-rare
exomes 47/1,435,252 · genomes 38/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0914% | 1,094 |
| Admixed American | 0.0152% | 6,569 |
| Remaining individualsnot grpmax-eligible | 0.00811% | 12,328 |
| South Asian | 0.00113% | 88,690 |
| European (non-Finnish) | 0.000173% | 579,519 |
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.Ser296=
- Coding
- c.888T>C
- MANE Select
- NM_001354930
- dbSNP
- rs113602774
- Type
- single nucleotide variant
- Location
- chr6:3089630 (GRCh38)
- Gene constraint
- LOEUF 0.6 · pLI 0.21 (gnomAD)
- Structure
- AlphaFold pLDDT 70.38 · 39 PDB
- Residue 296
- the 'interaction with sqstm1' region; an α-helix
Similar variants
- RIPK1 p.Ser296Arg 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-ser296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown