MLKL p.Leu294=
c.880C>T · rs80226077 · VCV791336
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.06%, afr)
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 3.2 | GERP -0.46, phastCons 1 |
| Overall | ||
| CADD | 6.353 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.06%
African / African-American · 1,546/75,006 alleles
Filtering AF
1.98%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.94%
Overall
0.104%
1,685/1,614,104 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.06% | 49 |
| Remaining individualsnot grpmax-eligible | 0.115% | 868 |
| Admixed American | 0.0916% | 1,091 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.0022% | 45,540 |
| European (non-Finnish) | 0.000763% | 131,113 |
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.Leu294=
- Coding
- c.880C>T
- MANE Select
- NM_152649
- dbSNP
- rs80226077
- Type
- single nucleotide variant
- Location
- chr16:74682727 (GRCh38)
- Gene constraint
- LOEUF 1.194 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.25 · 22 PDB
- Residue 294
- the protein kinase domain; an α-helix
Similar variants
- MLKL p.Asp100Glu Benign ★★ same type
- MLKL p.Lys234= 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
- MLKL p.Arg421Cys 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-leu294 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown