Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 30.8%, mid) — too common for a highly-penetrant pathogenic allele
Conditions
3
inherited retinal dystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.041 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.4 | GERP -2.7 |
| Overall | ||
| CADD | 8.717 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
30.8%
Middle Eastern · 1,864/6,060 alleles
Filtering AF
30%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 30%
Overall
27.4%
442,559/1,613,214 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 30.8% | 3 |
| European (non-Finnish) | 30.1% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 29.1% | 3 |
| Remaining individualsnot grpmax-eligible | 27% | 4 |
| South Asian | 22.2% | 5 |
| Finnishnot grpmax-eligible | 20.5% | 5 |
| Admixed American | 18% | 6 |
| African / African-American | 13.6% | 7 |
| East Asian | 13% | 8 |
| Amishnot grpmax-eligible | 10.5% | 10 |
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.Asn498=
- Coding
- c.1494C>T
- MANE Select
- NM_006343
- dbSNP
- rs3811634
- Type
- single nucleotide variant
- Location
- chr2:111997366 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.78 · 42 PDB
- Residue 498
- a UniProt-annotated variant site (in)
Similar variants
- MERTK p.Asn498Ser Benign/Likely benign ★★ same residue
- MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same condition
- MERTK c.1605-2A>G Pathogenic ★★ same condition
- MERTK c.1867+1G>A Likely pathogenic ★★ same condition
- MERTK c.1868-1G>A Pathogenic ★★ same condition
- MERTK c.2189+1G>T Pathogenic ★★ same condition
- MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ same condition
- MERTK p.Ala768Val Likely pathogenic ★★ same condition
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-asn498 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown