MKRN3 p.Ala75=
c.225C>T · rs759117637 · VCV732331
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0533%, amr)
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 -4.5 | GERP -2.9 |
| Overall | ||
| CADD | 3.217 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0533%
Admixed American · 32/60,018 alleles
Filtering AF
0.0387%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0339%
Overall
0.00211%
34/1,613,764 alleles · ultra-rare
exomes 9/1,461,562 · genomes 25/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0533% | 1,876 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00133% | 74,952 |
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.Ala75=
- Coding
- c.225C>T
- MANE Select
- NM_005664
- dbSNP
- rs759117637
- Type
- single nucleotide variant
- Location
- chr15:23566007 (GRCh38)
- Gene constraint
- LOEUF 1.665 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 64.59 · 1 PDB
- Residue 75
- the 'disordered' region
Similar variants
- MKRN3 c.-81C>T Uncertain significance ★★ same type
- MKRN3 p.Arg345His Uncertain significance ★★ ⚠ same type
- MKRN3 p.Gly172Asp Uncertain significance ★★ ⚠ same type
- MKRN3 p.His496Arg Uncertain significance ★★ ⚠ same type
- MKRN3 p.Thr145Met Uncertain significance ★★ ⚠ same type
- MKRN3 p.Gly131= Benign/Likely benign ★★ same type
- MKRN3 p.His119= Likely benign ★★ same type
- MKRN3 p.Pro134= Benign/Likely benign ★★ 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-ala75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown