MKRN3 p.Cys266=
c.798C>T · rs145255803 · VCV3050081
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0801%, afr)
Conditions
1
MKRN3-related disorder
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 -0.8 | GERP -1, phastCons 0.008 |
| Overall | ||
| CADD | 6.986 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0801%
African / African-American · 60/74,908 alleles
Filtering AF
0.0638%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.058%
Overall
0.00774%
125/1,613,990 alleles · ultra-rare
exomes 93/1,461,886 · genomes 32/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0801% | 1,248 |
| South Asian | 0.0318% | 3,141 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| Admixed American | 0.005% | 19,997 |
| Finnishnot grpmax-eligible | 0.00312% | 32,009 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.00195% | 51,305 |
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
- MKRN3
- Protein
- p.Cys266=
- Coding
- c.798C>T
- MANE Select
- NM_005664
- dbSNP
- rs145255803
- Type
- single nucleotide variant
- Location
- chr15:23566580 (GRCh38)
- Gene constraint
- LOEUF 1.665 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 64.59 · 1 PDB
- Residue 266
- the 'makorin-type cys-his' region
Disease context
MKRN3-related disorder
Similar variants
- MKRN3 p.Phe206= Likely benign same condition
- MKRN3 p.Ser38= Likely benign same condition
- MKRN3 p.Thr145= Likely benign same condition
- MKRN3 p.Ala288fs Pathogenic/Likely pathogenic ★★ same condition
- MKRN3 p.Ala162fs Conflicting classifications of pathogenicity ★ same condition
- MKRN3 c.-81C>T Uncertain significance ★★ same type
- MKRN3 p.Arg345His Uncertain significance ★★ ⚠ same type
- MKRN3 p.Gly172Asp Uncertain significance ★★ ⚠ 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/mkrn3-p-cys266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown