MEF2A p.Pro433del
c.1284GCC[2] · rs759657998 · VCV3250510
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.474%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.46 | phastCons 0.003 |
| Overall | ||
| CADD | 4.327 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | (CAG)n simple repeat · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.474%
European (non-Finnish) · 4,787/1,009,058 alleles
Filtering AF
0.463%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.459%
Overall
0.394%
5,443/1,379,868 alleles · rare
exomes 5,039/1,239,642 · genomes 404/140,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.474% | 211 |
| Remaining individualsnot grpmax-eligible | 0.378% | 264 |
| Middle Eastern | 0.322% | 310 |
| East Asian | 0.286% | 350 |
| Admixed American | 0.164% | 609 |
| Finnishnot grpmax-eligible | 0.142% | 704 |
| African / African-American | 0.121% | 829 |
| South Asian | 0.0988% | 1,012 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0703% | 1,421 |
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.Pro433del
- Coding
- c.1284GCC[2]
- MANE Select
- NM_001319206
- dbSNP
- rs759657998
- Type
- Microsatellite
- Location
- chr15:99712537 (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.Pro433Ser Uncertain significance ★ same residue
- MEF2A p.Gln427_Gln428dup Benign ★★ same type
- MEF2A p.Gln423_Gln428del Conflicting classifications of pathogenicity ★ same type
- MEF2A p.Gln427_Gln428del Benign ★ same type
- MEF2A p.Cys41_Glu42delinsTer Uncertain significance same type
- MEF2A p.Gln424_Gln428del 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/mef2a-p-pro433del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown