MARK4 p.Leu226=
c.678G>A · rs34784381 · VCV782650
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.75%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.86 | GERP -4.9 |
| Overall | ||
| CADD | 6.348 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.75%
African / African-American · 4,317/75,058 alleles
Filtering AF
5.61%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.55%
Overall
0.299%
4,825/1,614,248 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.75% | 17 |
| Remaining individualsnot grpmax-eligible | 0.342% | 292 |
| Admixed American | 0.332% | 302 |
| Middle Eastern | 0.28% | 357 |
| South Asian | 0.011% | 9,109 |
| European (non-Finnish) | 0.00576% | 17,354 |
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
- MARK4
- Protein
- p.Leu226=
- Coding
- c.678G>A
- MANE Select
- NM_001199867
- dbSNP
- rs34784381
- Type
- single nucleotide variant
- Location
- chr19:45271600 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.97 · 2 PDB
- Residue 226
- the protein kinase domain; an α-helix
Similar variants
- MARK4 p.Thr461= Benign ★★ same type
- MARK4 p.Ala168Ser Uncertain significance ★ ⚠ same type
- MARK4 p.Ala389Val Uncertain significance ★ ⚠ same type
- MARK4 p.Ala457Val Uncertain significance ★ ⚠ same type
- MARK4 p.Ala462Val Uncertain significance ★ ⚠ same type
- MARK4 p.Ala479Thr Uncertain significance ★ ⚠ same type
- MARK4 p.Ala47Thr Uncertain significance ★ ⚠ same type
- MARK4 p.Ala485Ser 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/mark4-p-leu226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown