MEF2C p.Ser334=
c.1002T>C · rs2152208828 · VCV1534763
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000176%, nfe)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP 0.018, phastCons 0.99 |
| Overall | ||
| CADD | 8.431 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000176%
European (non-Finnish) · 2/1,135,096 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000131%
2/1,530,430 alleles · very rare
exomes 2/1,378,112 · genomes 0/152,318 · 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.Ser334=
- Coding
- c.1002T>C
- MANE Select
- NM_002397
- dbSNP
- rs2152208828
- Type
- single nucleotide variant
- Location
- chr5:88728591 (GRCh38)
- Gene constraint
- LOEUF 0.212 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.80
Similar variants
- MEF2C p.Ser334fs Pathogenic ★ 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-ser334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown