MLKL p.Pro411=
c.1233G>A · VCV3295184
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0307%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -3.4 |
| Overall | ||
| CADD | 1.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0307%
African / African-American · 23/74,922 alleles
Filtering AF
0.021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0178%
Overall
0.00273%
44/1,614,044 alleles · ultra-rare
exomes 28/1,461,854 · genomes 16/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0307% | 3,257 |
| Middle Eastern | 0.0164% | 6,084 |
| South Asian | 0.00878% | 11,387 |
| East Asian | 0.00445% | 22,451 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 0.000678% | 147,504 |
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.Pro411=
- Coding
- c.1233G>A
- MANE Select
- NM_152649
- Type
- single nucleotide variant
- Location
- chr16:74675362 (GRCh38)
- Gene constraint
- LOEUF 1.194 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.25 · 22 PDB
- Residue 411
- the protein kinase domain; a turn
Similar variants
- MLKL p.Pro411Leu Uncertain significance ★ ⚠ same residue
- MLKL p.Asp100Glu Benign ★★ same type
- MLKL p.Leu294= 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
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-pro411 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown