Is MEF2C p.Thr60= (c.180C>T) pathogenic?

MEF2C p.Thr60= (c.180C>T) is classified Benign/Likely benign in MEF2C (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-12). Rare (popmax 0.242%, amr); Associated with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language.

How common is MEF2C p.Thr60= (c.180C>T) in the general population?

MEF2C p.Thr60= (c.180C>T) is rare (popmax 0.242%, amr) (gnomAD).

MEF2C p.Thr60=

Q: What condition is associated with MEF2C p.Thr60= (c.180C>T)?

MEF2C p.Thr60= (c.180C>T) is associated with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (ClinVar).

c.180C>T · rs773278207 · VCV487206

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.242%, amr)

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 -3.7	GERP -4.8
Overall
CADD	11.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.242% Admixed American · 145/59,980 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.197%

Overall 0.00991% 160/1,613,946 alleles · rare exomes 145/1,461,874 · genomes 15/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.242%	414
Remaining individualsnot grpmax-eligible	0.008%	12,496
African / African-American	0.00401%	24,961
East Asian	0.00223%	44,886
South Asian	0.0022%	45,542
European (non-Finnish)	0.000339%	295,004

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.Thr60=
Coding: c.180C>T
MANE Select: NM_002397
dbSNP: rs773278207
Type: single nucleotide variant
Location: chr5:88804676 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.80
Residue 60: a DNA-binding 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 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-thr60 (accessed [today's date]).

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