MEF2A p.Pro433Ser
c.1297C>T · rs778137086 · VCV2465526
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0687%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.117 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.25 | |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 41 kb · p 0.25 · regional, not allelic |
| Overall | ||
| CADD | 4.586 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0687%
East Asian · 28/40,764 alleles
Filtering AF
0.0488%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0421%
Overall
0.00193%
30/1,550,434 alleles · ultra-rare
exomes 25/1,398,240 · genomes 5/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0687% | 1,456 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,029 |
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.Pro433Ser
- Coding
- c.1297C>T
- MANE Select
- NM_001319206
- dbSNP
- rs778137086
- Type
- single nucleotide variant
- Location
- chr15:99712550 (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.Pro433= Benign ★★ 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-pro433ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown