MEF2A p.Pro135Ser
c.403C>T · rs748952164 · VCV2391955
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0281%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.308 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 6 | phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 41 kb · p 0.25 · regional, not allelic |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0281%
African / African-American · 21/74,858 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00186%
30/1,609,356 alleles · ultra-rare
exomes 13/1,457,162 · genomes 17/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0281% | 3,565 |
| East Asian | 0.00893% | 11,197 |
| Remaining individualsnot grpmax-eligible | 0.00642% | 15,577 |
| European (non-Finnish) | 8.5e-05% | 1,176,262 |
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.Pro135Ser
- Coding
- c.403C>T
- MANE Select
- NM_001319206
- dbSNP
- rs748952164
- Type
- single nucleotide variant
- Location
- chr15:99674405 (GRCh38)
- Gene constraint
- LOEUF 0.762 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.90 · 10 PDB
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-pro135ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown