MERTK p.Phe742=
c.2226C>T · rs760532027 · VCV1670125
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.53 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.1 | GERP -3.4 |
| Overall | ||
| CADD | 7.247 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
Middle Eastern · 1/5,946 alleles
Filtering AF
0.00291%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0026%
Overall
0.00372%
60/1,613,632 alleles · ultra-rare
exomes 58/1,461,490 · genomes 2/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0168% | 5,946 |
| Finnishnot grpmax-eligible | 0.0125% | 8,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,814 |
| European (non-Finnish) | 0.00381% | 26,219 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Admixed American | 0.00333% | 29,996 |
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.Phe742=
- Coding
- c.2226C>T
- MANE Select
- NM_006343
- dbSNP
- rs760532027
- Type
- single nucleotide variant
- Location
- chr2:112021458 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.78 · 42 PDB
- Residue 742
- the protein kinase domain
Similar variants
- 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
- MERTK p.Ala768Val 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-phe742 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown