MERTK p.Ile631=
c.1893C>T · rs543947091 · VCV1125036
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0527%, sas)
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 -2.1 | GERP -3.7 |
| Overall | ||
| CADD | 8.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0527%
South Asian · 48/91,074 alleles
Filtering AF
0.0408%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0366%
Overall
0.00527%
85/1,613,902 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0527% | 1,897 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,830 |
| East Asian | 0.00446% | 22,441 |
| African / African-American | 0.00267% | 37,510 |
| European (non-Finnish) | 0.00254% | 39,328 |
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.Ile631=
- Coding
- c.1893C>T
- MANE Select
- NM_006343
- dbSNP
- rs543947091
- Type
- single nucleotide variant
- Location
- chr2:112008408 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.78 · 42 PDB
- Residue 631
- an α-helix; the protein kinase domain
Similar variants
- MERTK p.Ile631Met 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-ile631 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown