MLKL p.Lys234=
c.702A>G · rs56247416 · VCV716578
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.11%, amr)
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 | GERP -4.5 |
| Overall | ||
| CADD | 0.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.11%
Admixed American · 1,221/57,766 alleles
Filtering AF
2.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.98%
Overall
0.0933%
1,491/1,598,684 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 2.11% | 47 |
| East Asian | 0.219% | 457 |
| Remaining individualsnot grpmax-eligible | 0.123% | 814 |
| African / African-American | 0.0562% | 1,780 |
| South Asian | 0.0156% | 6,390 |
| European (non-Finnish) | 0.00366% | 27,286 |
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
- MLKL
- Protein
- p.Lys234=
- Coding
- c.702A>G
- MANE Select
- NM_152649
- dbSNP
- rs56247416
- Type
- single nucleotide variant
- Location
- chr16:74691297 (GRCh38)
- Gene constraint
- LOEUF 1.194 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.25 · 22 PDB
- Residue 234
- the protein kinase domain
Similar variants
- MLKL p.Lys234Ile Uncertain significance ★ ⚠ same residue
- MLKL p.Asp100Glu Benign ★★ same type
- MLKL p.Leu294= Benign ★★ same type
- MLKL p.Ala406Thr Uncertain significance ★ ⚠ same type
- MLKL p.Ala450Val Uncertain significance ★ ⚠ same type
- MLKL p.Arg121Leu Uncertain significance ★ ⚠ same type
- MLKL p.Arg145Thr Uncertain significance ★ ⚠ same type
- MLKL p.Arg306Cys 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/mlkl-p-lys234 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown