MEF2A p.Pro433=
c.1299G>A · rs367780642 · VCV779963
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.94%, eas)
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 -5.9 | |
| Overall | ||
| CADD | 0.472 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.94%
East Asian · 1,198/40,756 alleles
Filtering AF
2.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.75%
Overall
0.116%
1,798/1,549,988 alleles · low-frequency
exomes 1,514/1,398,170 · genomes 284/151,818 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 2.94% | 34 |
| Admixed American | 0.515% | 194 |
| Remaining individualsnot grpmax-eligible | 0.311% | 321 |
| South Asian | 0.0632% | 1,583 |
| Middle Eastern | 0.0167% | 5,984 |
| African / African-American | 0.00959% | 10,423 |
| European (non-Finnish) | 0.00776% | 12,880 |
| Finnishnot grpmax-eligible | 0.00168% | 59,606 |
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.Pro433=
- Coding
- c.1299G>A
- MANE Select
- NM_001319206
- dbSNP
- rs367780642
- Type
- single nucleotide variant
- Location
- chr15:99712552 (GRCh38)
- Gene constraint
- LOEUF 0.762 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.90 · 10 PDB
- Residue 433
- the 'disordered' region
Similar variants
- MEF2A p.Pro433Ser Uncertain significance ★ same residue
- MEF2A p.Pro433del Likely benign ★ same residue
- MEF2A p.Asn261Ser Benign/Likely benign ★★ same type
- MEF2A p.Ile479Val Benign/Likely 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
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-pro433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown