MERTK p.Arg584=
c.1750A>C · rs199937492 · VCV728066
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0584%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.1 | GERP -0.55, phastCons 1 |
| Overall | ||
| CADD | 8.704 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0584%
Admixed American · 35/59,982 alleles
Filtering AF
0.0431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.00237%
38/1,601,038 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0584% | 1,714 |
| Remaining individualsnot grpmax-eligible | 0.00484% | 20,677 |
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
- MERTK
- Protein
- p.Arg584=
- Coding
- c.1750A>C
- MANE Select
- NM_006343
- dbSNP
- rs199937492
- Type
- single nucleotide variant
- Location
- chr2:112003151 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.78 · 42 PDB
- Residue 584
- an α-helix
Similar variants
- MERTK p.Arg584Ser Uncertain significance ★ ⚠ same residue
- MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same type
- MERTK c.1605-2A>G Pathogenic ★★ same type
- MERTK c.1787-2A>T Pathogenic/Likely pathogenic ★★ same type
- MERTK c.1867+1G>A Likely pathogenic ★★ same type
- MERTK c.1868-1G>A Pathogenic ★★ same type
- MERTK c.2189+1G>T Pathogenic ★★ same type
- MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ 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/mertk-p-arg584 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown