MARK2 p.Pro459=
c.1377C>A · rs56291692 · VCV711552
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.94%, 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 -14 | GERP -3.6 |
| Overall | ||
| CADD | 1.501 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.94%
African / African-American · 2,208/75,014 alleles
Filtering AF
2.84%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.8%
Overall
0.182%
2,933/1,613,662 alleles · low-frequency
exomes 1,574/1,461,388 · genomes 1,359/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.94% | 34 |
| Admixed American | 0.373% | 268 |
| Middle Eastern | 0.331% | 302 |
| Remaining individualsnot grpmax-eligible | 0.295% | 339 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0608% | 1,645 |
| European (non-Finnish) | 0.0231% | 4,338 |
| South Asian | 0.00878% | 11,384 |
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
- MARK2
- Protein
- p.Pro459=
- Coding
- c.1377C>A
- MANE Select
- NM_001039469
- dbSNP
- rs56291692
- Type
- single nucleotide variant
- Location
- chr11:63902743 (GRCh38)
- Gene constraint
- LOEUF 0.287 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.21 · 5 PDB
- Residue 459
- a UniProt-annotated variant site (in mrd76; likely pathogenic); a UniProt-annotated variant site (in mrd76; pathogenic); the 'disordered' region
Similar variants
- MARK2 p.Ala432Thr Uncertain significance ★★ ⚠ same type
- MARK2 p.Arg264Ser Uncertain significance ★★ ⚠ same type
- MARK2 p.Arg482Ter Uncertain significance ★★ same type
- MARK2 c.337+8C>G Likely benign ★★ same type
- MARK2 p.Pro740= Benign ★★ same type
- MARK2 p.Ser725= Benign ★★ same type
- MARK2 c.1102-1G>C Likely pathogenic ★ same type
- MARK2 c.1934+1G>A Likely pathogenic ★ 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/mark2-p-pro459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown