MKRN3 p.Pro134=
c.402G>A · rs149344478 · VCV723342
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.397%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.81 | GERP -3.3 |
| Overall | ||
| CADD | 3.849 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.397%
African / African-American · 298/75,070 alleles
Filtering AF
0.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.345%
Overall
0.0338%
546/1,613,782 alleles · rare
exomes 361/1,461,410 · genomes 185/152,372 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.397% | 252 |
| South Asian | 0.192% | 520 |
| Admixed American | 0.0283% | 3,531 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| East Asian | 0.00669% | 14,958 |
| European (non-Finnish) | 0.00314% | 31,892 |
| Finnishnot grpmax-eligible | 0.00157% | 63,632 |
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.Pro134=
- Coding
- c.402G>A
- MANE Select
- NM_005664
- dbSNP
- rs149344478
- Type
- single nucleotide variant
- Location
- chr15:23566184 (GRCh38)
- Gene constraint
- LOEUF 1.665 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 64.59 · 1 PDB
- Residue 134
- 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.Pro221= 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-pro134 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown