RIPK4 p.His123=
c.369C>T · rs367871385 · VCV739789
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0373%, sas)
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 -3.3 | GERP -5.1 |
| Overall | ||
| CADD | 2.305 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0373%
South Asian · 34/91,074 alleles
Filtering AF
0.0274%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.024%
Overall
0.00415%
67/1,614,006 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0373% | 2,679 |
| African / African-American | 0.02% | 5,003 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
| European (non-Finnish) | 0.00136% | 73,753 |
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.His123=
- Coding
- c.369C>T
- MANE Select
- NM_020639
- dbSNP
- rs367871385
- Type
- single nucleotide variant
- Location
- chr21:41756630 (GRCh38)
- Gene constraint
- LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 75.41
- Residue 123
- the protein kinase domain
Similar variants
- RIPK4 c.*1361T>A Uncertain significance ★★ same type
- RIPK4 p.Ala126Val Uncertain significance ★★ ⚠ same type
- RIPK4 p.Arg241Cys Uncertain significance ★★ ⚠ same type
- RIPK4 p.Arg260His Uncertain significance ★★ ⚠ same type
- RIPK4 p.Arg271Gln Uncertain significance ★★ ⚠ same type
- RIPK4 p.Arg320Gln Uncertain significance ★★ ⚠ same type
- RIPK4 p.Arg493Trp Uncertain significance ★★ ⚠ same type
- RIPK4 p.Arg521Trp 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/ripk4-p-his123 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown