MARK4 p.Thr461=
c.1383C>T · rs148301412 · VCV711221
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.472%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.025 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.8 |
| Overall | ||
| CADD | 0.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.472%
African / African-American · 352/74,570 alleles
Filtering AF
0.431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.415%
Overall
0.0311%
495/1,589,908 alleles · rare
exomes 268/1,437,580 · genomes 227/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.472% | 212 |
| Admixed American | 0.0944% | 1,060 |
| Remaining individualsnot grpmax-eligible | 0.0636% | 1,572 |
| Middle Eastern | 0.0334% | 2,998 |
| European (non-Finnish) | 0.00411% | 24,309 |
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
- MARK4
- Protein
- p.Thr461=
- Coding
- c.1383C>T
- MANE Select
- NM_001199867
- dbSNP
- rs148301412
- Type
- single nucleotide variant
- Location
- chr19:45287553 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.97 · 2 PDB
- Residue 461
- the 'disordered' region
Similar variants
- MARK4 p.Leu226= Benign ★★ same type
- MARK4 p.Ala168Ser Uncertain significance ★ ⚠ same type
- MARK4 p.Ala389Val Uncertain significance ★ ⚠ same type
- MARK4 p.Ala457Val Uncertain significance ★ ⚠ same type
- MARK4 p.Ala462Val Uncertain significance ★ ⚠ same type
- MARK4 p.Ala479Thr Uncertain significance ★ ⚠ same type
- MARK4 p.Ala47Thr Uncertain significance ★ ⚠ same type
- MARK4 p.Ala485Ser 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/mark4-p-thr461 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown