MARK3 p.Leu625=
c.1875T>C · rs372826694 · VCV3043460
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.415%, afr)
Conditions
1
MARK3-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.053 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.38 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.415%
African / African-American · 311/75,030 alleles
Filtering AF
0.377%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.362%
Overall
0.0228%
368/1,612,096 alleles · rare
exomes 199/1,459,738 · genomes 169/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.415% | 241 |
| Admixed American | 0.0518% | 1,929 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,673 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00551% | 18,159 |
| European (non-Finnish) | 0.000255% | 392,887 |
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
- MARK3
- Protein
- p.Leu625=
- Coding
- c.1875T>C
- MANE Select
- NM_001128918
- dbSNP
- rs372826694
- Type
- single nucleotide variant
- Location
- chr14:103500159 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.25 · 14 PDB
Disease context
MARK3-related disorder
Similar variants
- MARK3 c.1586+4G>C Likely benign same condition
- MARK3 c.412+4A>T Likely benign same condition
- MARK3 p.Ala431= Benign same condition
- MARK3 p.Asn632= Likely benign same condition
- MARK3 p.Gln50= Likely benign same condition
- MARK3 p.Gly296Arg Likely benign same condition
- MARK3 p.Lys463= Benign same condition
- MARK3 p.Ser443Gly Benign same condition
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/mark3-p-leu625 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown