Is MEF2A p.Pro439Ser (c.1315C>T) pathogenic?

MEF2A p.Pro439Ser (c.1315C>T) is classified Uncertain significance in MEF2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). Absent from gnomAD v4.1.

How common is MEF2A p.Pro439Ser (c.1315C>T) in the general population?

MEF2A p.Pro439Ser (c.1315C>T) is absent from gnomAD v4.1 (gnomAD).

MEF2A p.Pro439Ser

c.1315C>T · VCV4106302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.06	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	phastCons 0.033
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.25 · regional, not allelic
Overall
CADD	5.47	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: MEF2A
Protein: p.Pro439Ser
Coding: c.1315C>T
MANE Select: NM_001319206
Type: single nucleotide variant
Location: chr15:99712568 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.90 · 10 PDB
Residue 439: the 'disordered' region

Full MEF2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MEF2A p.Asn261Ser Benign/Likely benign ★★ same type
MEF2A p.Ile479Val Benign/Likely benign ★★ same type
MEF2A p.Pro433= Benign ★★ same type
MEF2A p.Pro277Leu Pathogenic ★ same type
MEF2A c.610+2T>A Uncertain significance ★ same type
MEF2A p.Ala502Thr Uncertain significance ★ same type
MEF2A p.Arg409Trp Uncertain significance ★ same type
MEF2A p.Arg411Cys 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/mef2a-p-pro439ser (accessed [today's date]).

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