MERTK p.Val476=
c.1428G>A · rs779952826 · VCV1670314
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00934%, afr)
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 5.8 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 6.923 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00934%
African / African-American · 7/74,916 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.000558%
9/1,614,054 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00934% | 10,702 |
| Admixed American | 0.00167% | 60,004 |
| European (non-Finnish) | 8.47e-05% | 1,180,048 |
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.Val476=
- Coding
- c.1428G>A
- MANE Select
- NM_006343
- dbSNP
- rs779952826
- Type
- single nucleotide variant
- Location
- chr2:111994382 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.78 · 42 PDB
- Residue 476
- a β-strand; the fibronectin type-iii 2 domain
Similar variants
- MERTK p.Val476Leu 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-val476 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown