Is MEF2C p.Asp83Val (c.248A>T) pathogenic?

MEF2C p.Asp83Val (c.248A>T) is classified Uncertain significance in MEF2C (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-12). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MEF2C p.Asp83Val (c.248A>T)?

MEF2C p.Asp83Val (c.248A>T) is associated with Inborn genetic diseases (ClinVar).

How common is MEF2C p.Asp83Val (c.248A>T) in the general population?

MEF2C p.Asp83Val (c.248A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MEF2C p.Asp83Val (c.248A>T)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

MEF2C p.Asp83Val

c.248A>T · VCV4839388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 7% in MEF2C
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -16.73	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.15	constrained · MANE · 63 kb · p 1.7e-23 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Asp83Val
Coding: c.248A>T
MANE Select: NM_002397
Type: single nucleotide variant
Location: chr5:88804608 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.80
Residue 83: a DNA-binding 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

Similar variants

MEF2C p.Asp83= Likely benign ★ same residue
MEF2C c.638-2A>C Pathogenic ★★ same condition
MEF2C p.Arg189Ter Pathogenic/Likely pathogenic ★★ same condition
MEF2C p.Leu38Pro Pathogenic ★★ same condition
MEF2C p.Gly185Ser Uncertain significance ★★ ⚠ same condition
MEF2C p.Met12Val Uncertain significance ★★ ⚠ same condition
MEF2C p.Pro219Thr Uncertain significance ★★ ⚠ same condition
MEF2C p.Ala103= Likely benign ★★ 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-asp83val (accessed [today's date]).

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