MEF2A p.Gln428Pro
c.1283A>C · VCV4083646
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.136%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.093 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.46 | phastCons 0.003 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 41 kb · p 0.25 · regional, not allelic |
| Overall | ||
| CADD | 0.019 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.136%
African / African-American · 91/67,148 alleles
Filtering AF
0.113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.105%
Overall
0.0125%
173/1,380,068 alleles · rare
exomes 115/1,239,832 · genomes 58/140,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.136% | 738 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0444% | 2,253 |
| South Asian | 0.0165% | 6,074 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,744 |
| European (non-Finnish) | 0.00466% | 21,473 |
| Admixed American | 0.00427% | 23,429 |
| East Asian | 0.00289% | 34,606 |
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
- MEF2A
- Protein
- p.Gln428Pro
- Coding
- c.1283A>C
- MANE Select
- NM_001319206
- Type
- single nucleotide variant
- Location
- chr15:99712536 (GRCh38)
- Gene constraint
- LOEUF 0.762 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.90 · 10 PDB
- Residue 428
- the 'disordered' region
Similar variants
- MEF2A p.Asn261Ser Benign/Likely benign ★★ same type
- MEF2A p.Ile479Val Benign/Likely benign ★★ same type
- MEF2A p.Pro433= Benign ★★ same type
- MEF2A p.Pro277Leu Pathogenic ★ same type
- MEF2A c.610+2T>A Uncertain significance ★ same type
- MEF2A p.Ala502Thr Uncertain significance ★ same type
- MEF2A p.Arg409Trp Uncertain significance ★ same type
- MEF2A p.Arg411Cys 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/mef2a-p-gln428pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown