Is MEF2C p.Ser453= (c.1359G>T) pathogenic?

MEF2C p.Ser453= (c.1359G>T) is classified Likely benign in MEF2C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language.

How common is MEF2C p.Ser453= (c.1359G>T) in the general population?

MEF2C p.Ser453= (c.1359G>T) is absent from gnomAD v4.1 (gnomAD).

MEF2C p.Ser453=

Q: What condition is associated with MEF2C p.Ser453= (c.1359G>T)?

MEF2C p.Ser453= (c.1359G>T) is associated with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (ClinVar).

c.1359G>T · rs1224709005 · VCV1159640

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Overall
CADD	14.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MEF2C
Protein: p.Ser453=
Coding: c.1359G>T
MANE Select: NM_002397
dbSNP: rs1224709005
Type: single nucleotide variant
Location: chr5:88722667 (GRCh38)

Full MEF2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser453 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown