Is MEF2D p.Ala200Pro (c.598G>C) pathogenic?

MEF2D p.Ala200Pro (c.598G>C) is classified Uncertain significance in MEF2D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely benign (0.1539); Absent from gnomAD v4.1; Associated with MEF2D-related disorder.

What condition is associated with MEF2D p.Ala200Pro (c.598G>C)?

MEF2D p.Ala200Pro (c.598G>C) is associated with MEF2D-related disorder (ClinVar).

How common is MEF2D p.Ala200Pro (c.598G>C) in the general population?

MEF2D p.Ala200Pro (c.598G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MEF2D p.Ala200Pro (c.598G>C)?

AlphaMissense predicts likely benign (score 0.1539) — an in-silico prediction, not a clinical call.

MEF2D p.Ala200Pro

c.598G>C · rs2525111171 · VCV2629869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1539 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MEF2D-related disorder

Computational evidence

Protein change
AlphaMissense	0.1539	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP -0.53, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 15 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: MEF2D
Protein: p.Ala200Pro
Coding: c.598G>C
MANE Select: NM_005920
dbSNP: rs2525111171
Type: single nucleotide variant
Location: chr1:156479595 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.81 · 2 PDB
Residue 200: the 'disordered' region

Full MEF2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MEF2D-related disorder

Similar variants

MEF2D p.Ala452Val Uncertain significance ★ ⚠ same type
MEF2D p.Arg24Gln Uncertain significance ★ ⚠ same type
MEF2D p.Arg487Gln Uncertain significance ★ ⚠ same type
MEF2D p.Arg487Trp Uncertain significance ★ ⚠ same type
MEF2D p.Asn241Asp Uncertain significance ★ ⚠ same type
MEF2D p.Asn52Lys Uncertain significance ★ ⚠ same type
MEF2D p.Asp97Asn Uncertain significance ★ ⚠ same type
MEF2D p.Gln182Lys Uncertain significance ★ ⚠ same type

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/mef2d-p-ala200pro (accessed [today's date]).

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