MARK3 p.Ala431=
c.1293G>A · rs142938235 · VCV3033292
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 1%, afr)
Conditions
1
MARK3-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.056 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -5.5 |
| Overall | ||
| CADD | 5.657 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1%
African / African-American · 750/75,012 alleles
Filtering AF
0.94%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.917%
Overall
0.0541%
873/1,613,916 alleles · rare
exomes 453/1,461,672 · genomes 420/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1% | 100 |
| Remaining individualsnot grpmax-eligible | 0.0768% | 1,302 |
| Admixed American | 0.0633% | 1,579 |
| South Asian | 0.022% | 4,553 |
| East Asian | 0.0111% | 8,978 |
| Finnishnot grpmax-eligible | 0.00312% | 32,008 |
| European (non-Finnish) | 0.000848% | 117,984 |
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.Ala431=
- Coding
- c.1293G>A
- MANE Select
- NM_001128918
- dbSNP
- rs142938235
- Type
- single nucleotide variant
- Location
- chr14:103475021 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.25 · 14 PDB
- Residue 431
- the 'disordered' region
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.Asn632= Likely benign same condition
- MARK3 p.Gln50= Likely benign same condition
- MARK3 p.Gly296Arg Likely benign same condition
- MARK3 p.Leu625= 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-ala431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown