MARK4 p.Glu638=
c.1914G>A · VCV4104157
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0118%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.209 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 11.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0118%
European (non-Finnish) · 139/1,174,354 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0096%
Overall
0.00897%
144/1,605,318 alleles · ultra-rare
exomes 141/1,453,124 · genomes 3/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0118% | 8,449 |
| Remaining individualsnot grpmax-eligible | 0.00645% | 15,495 |
| East Asian | 0.00225% | 44,412 |
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.Glu638=
- Coding
- c.1914G>A
- MANE Select
- NM_001199867
- Type
- single nucleotide variant
- Location
- chr19:45299847 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.97 · 2 PDB
Similar variants
- MARK4 p.Leu226= Benign ★★ same type
- MARK4 p.Thr461= 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
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-glu638 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown