MARK1 p.Phe257=
c.771C>T · rs56188826 · VCV779300
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.321%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5 | GERP -3.7 |
| Overall | ||
| CADD | 1.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.321%
European (non-Finnish) · 3,782/1,179,936 alleles
Filtering AF
0.312%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.309%
Overall
0.255%
4,111/1,613,992 alleles · rare
exomes 3,900/1,461,758 · genomes 211/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.321% | 312 |
| Remaining individualsnot grpmax-eligible | 0.211% | 474 |
| Admixed American | 0.112% | 896 |
| South Asian | 0.0857% | 1,167 |
| African / African-American | 0.0413% | 2,420 |
| Finnishnot grpmax-eligible | 0.0266% | 3,765 |
| Middle Eastern | 0.0165% | 6,062 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,802 |
| East Asian | 0.00223% | 44,876 |
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
- MARK1
- Protein
- p.Phe257=
- Coding
- c.771C>T
- MANE Select
- NM_018650
- dbSNP
- rs56188826
- Type
- single nucleotide variant
- Location
- chr1:220618528 (GRCh38)
- Gene constraint
- LOEUF 0.577 · pLI 0.33 (gnomAD)
- Structure
- AlphaFold pLDDT 68.33 · 3 PDB
- Residue 257
- the protein kinase domain
Similar variants
- MARK1 p.Arg577Gln Uncertain significance ★★ ⚠ same type
- MARK1 p.Ala541Pro Benign ★★ same type
- MARK1 p.Ala352Thr Uncertain significance ★ ⚠ same type
- MARK1 p.Ala442Asp Uncertain significance ★ ⚠ same type
- MARK1 p.Arg268Gln Uncertain significance ★ ⚠ same type
- MARK1 p.Arg391Gln Uncertain significance ★ ⚠ same type
- MARK1 p.Arg421Cys Uncertain significance ★ ⚠ same type
- MARK1 p.Arg42Trp 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/mark1-p-phe257 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown