RIPK4 p.His240=
c.720C>T · VCV3352976
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0435%, amr)
Conditions
1
RIPK4-related disorder
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 5.6 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 11.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0435%
Admixed American · 26/59,714 alleles
Filtering AF
0.0305%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0261%
Overall
0.0018%
29/1,608,602 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0435% | 2,297 |
| European (non-Finnish) | 0.000255% | 392,889 |
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
- RIPK4
- Protein
- p.His240=
- Coding
- c.720C>T
- MANE Select
- NM_020639
- Type
- single nucleotide variant
- Location
- chr21:41746725 (GRCh38)
- Gene constraint
- LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 75.41
- Residue 240
- the protein kinase domain
Disease context
RIPK4-related disorder
Similar variants
- RIPK4 p.Val272Leu Uncertain significance ★ ⚠ same condition
- RIPK4 p.Ala611= Likely benign same condition
- RIPK4 p.Arg614= Likely benign same condition
- RIPK4 p.Gln769= Likely benign same condition
- RIPK4 p.His547= Likely benign same condition
- RIPK4 p.Ile414= Likely benign same condition
- RIPK4 p.Leu523= Likely benign same condition
- RIPK4 p.Ser337= Likely benign same condition
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/ripk4-p-his240 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown