MEF2C p.Val161=
c.483C>A · VCV4811738
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 7.5 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 12.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,942 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000124%
2/1,613,896 alleles · very rare
exomes 0/1,461,680 · genomes 2/152,216 · joint denominator
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.Val161=
- Coding
- c.483C>A
- MANE Select
- NM_002397
- Type
- single nucleotide variant
- Location
- chr5:88751963 (GRCh38)
- Gene constraint
- LOEUF 0.212 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.80
Similar variants
- 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
- MEF2C p.Arg15Pro 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-val161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown