MARK2 p.Leu346fs
c.1036dup · VCV3378099
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -4.8 | GERP -3.8 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MARK2
- Protein
- p.Leu346fs
- Coding
- c.1036dup
- MANE Select
- NM_001039469
- Type
- Duplication
- Location
- chr11:63901003 (GRCh38)
- Gene constraint
- LOEUF 0.287 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.21 · 5 PDB
- Residue 346
- the uba domain; a UniProt-annotated variant site (in mrd76; likely pathogenic); a UniProt-annotated variant site (in mrd76; pathogenic); an α-helix
Similar variants
- MARK2 p.Gly580fs Pathogenic ★ same type
- MARK2 p.Tyr215Ter Likely pathogenic ★ same type
- MARK2 p.Tyr267Ter Pathogenic ★ same type
- MARK2 p.Ala630fs Uncertain significance ★ same type
- MARK2 p.Arg589fs Uncertain significance ★ same type
- MARK2 p.Asn421Ter Uncertain significance ★ same type
- MARK2 p.Glu120Ter Uncertain significance ★ same type
- MARK2 p.Ile634fs 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/mark2-p-leu346fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown