MKRN3 p.Arg351=
c.1053A>G · VCV4923497
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00833%, 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 0.11 | GERP -3.7 |
| Overall | ||
| CADD | 0.798 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,034 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00206%
Overall
0.000496%
8/1,614,228 alleles · very rare
exomes 8/1,461,892 · genomes 0/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,007 |
| South Asian | 0.0011% | 91,088 |
| European (non-Finnish) | 0.000169% | 590,019 |
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.Arg351=
- Coding
- c.1053A>G
- MANE Select
- NM_005664
- Type
- single nucleotide variant
- Location
- chr15:23566835 (GRCh38)
- Gene constraint
- LOEUF 1.665 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 64.59 · 1 PDB
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-arg351 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown