RIPK1 p.Ser25=
c.75C>T · rs756198478 · VCV2200552
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
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 -13 | GERP -4 |
| Overall | ||
| CADD | 6.111 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,792 alleles
Filtering AF
0.00727%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00472%
76/1,609,200 alleles · ultra-rare
exomes 73/1,458,072 · genomes 3/151,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,399 |
| European (non-Finnish) | 0.0051% | 19,611 |
| African / African-American | 0.00403% | 24,795 |
| South Asian | 0.0033% | 30,305 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,150 |
| Admixed American | 0.00167% | 59,864 |
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.Ser25=
- Coding
- c.75C>T
- MANE Select
- NM_001354930
- dbSNP
- rs756198478
- Type
- single nucleotide variant
- Location
- chr6:3076898 (GRCh38)
- Gene constraint
- LOEUF 0.6 · pLI 0.21 (gnomAD)
- Structure
- AlphaFold pLDDT 70.38 · 39 PDB
- Residue 25
- the protein kinase domain; a binding site; a modified residue (phosphoserine; by ikka and ikkb)
Similar variants
- 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
- RIPK1 p.Ala220Thr 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-ser25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown