Is MEF2C p.Ala103= (c.309G>A) pathogenic?

MEF2C p.Ala103= (c.309G>A) is classified Likely benign in MEF2C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-29). Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with MEF2C p.Ala103= (c.309G>A)?

MEF2C p.Ala103= (c.309G>A) is associated with Inborn genetic diseases, neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (ClinVar).

How common is MEF2C p.Ala103= (c.309G>A) in the general population?

MEF2C p.Ala103= (c.309G>A) is very rare (popmax 0.004%, afr) (gnomAD).

MEF2C p.Ala103=

c.309G>A · rs567797470 · VCV1145008

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Inborn genetic diseases

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 -1.5	GERP -4.4
Overall
CADD	12.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,052 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00229% 37/1,613,978 alleles · very rare exomes 27/1,461,688 · genomes 10/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,017
South Asian	0.00329%	30,362
European (non-Finnish)	0.00246%	40,685
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Ala103=
Coding: c.309G>A
MANE Select: NM_002397
dbSNP: rs567797470
Type: single nucleotide variant
Location: chr5:88761278 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.80
Residue 103: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

Similar variants

MEF2C p.Ala103Val Conflicting classifications of pathogenicity ★ ⚠ same residue
MEF2C p.Ala103Glu 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

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-ala103 (accessed [today's date]).

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