Is MEF2C p.Arg189= (c.565C>A) pathogenic?

MEF2C p.Arg189= (c.565C>A) is classified Likely benign in MEF2C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-18). Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language.

How common is MEF2C p.Arg189= (c.565C>A) in the general population?

MEF2C p.Arg189= (c.565C>A) is absent from gnomAD v4.1 (gnomAD).

MEF2C p.Arg189=

Q: What condition is associated with MEF2C p.Arg189= (c.565C>A)?

MEF2C p.Arg189= (c.565C>A) is associated with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (ClinVar).

c.565C>A · VCV3653772

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

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 5.6	GERP 0.74, phastCons 1
Overall
CADD	12.75	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.Arg189=
Coding: c.565C>A
MANE Select: NM_002397
Type: single nucleotide variant
Location: chr5:88751881 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.80
Residue 189: the 'disordered' region

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

Similar variants

MEF2C p.Arg189Ter Pathogenic/Likely pathogenic ★★ same residue
MEF2C p.Arg189Leu Uncertain significance ★ ⚠ same residue
MEF2C p.Arg189Gln Likely benign ★ 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

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-arg189 (accessed [today's date]).

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