MEF2C p.Pro160=
c.480T>C · rs200518765 · VCV2433730
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.078%, eas)
Conditions
1
neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -5 |
| Overall | ||
| CADD | 2.396 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.078%
East Asian · 35/44,882 alleles
Filtering AF
0.0576%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0506%
Overall
0.00223%
36/1,614,036 alleles · ultra-rare
exomes 35/1,461,684 · genomes 1/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.078% | 1,282 |
| Admixed American | 0.00167% | 60,028 |
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
- MEF2C
- Protein
- p.Pro160=
- Coding
- c.480T>C
- MANE Select
- NM_002397
- dbSNP
- rs200518765
- Type
- single nucleotide variant
- Location
- chr5:88751966 (GRCh38)
- Gene constraint
- LOEUF 0.212 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.80
Similar variants
- MEF2C p.Pro160Ser Uncertain significance ★ ⚠ same residue
- MEF2C c.638-1G>A Pathogenic/Likely pathogenic ★★ same condition
- MEF2C c.638-2A>C Pathogenic ★★ same condition
- MEF2C c.965-2A>G Pathogenic ★★ same condition
- MEF2C c.-26C>T Pathogenic ★★ same condition
- MEF2C c.-8C>T Pathogenic ★★ same condition
- MEF2C p.Arg15Cys Pathogenic/Likely pathogenic ★★ same condition
- MEF2C p.Arg15His Pathogenic/Likely pathogenic ★★ same condition
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/mef2c-p-pro160 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown