Is MEF2A p.Pro331= (c.993G>A) pathogenic?

MEF2A p.Pro331= (c.993G>A) is classified Likely benign in MEF2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). Very rare (popmax 0.005%, amr).

How common is MEF2A p.Pro331= (c.993G>A) in the general population?

MEF2A p.Pro331= (c.993G>A) is very rare (popmax 0.005%, amr) (gnomAD).

MEF2A p.Pro331=

c.993G>A · VCV3872089

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -9.5
Overall
CADD	1.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000991% 16/1,613,846 alleles · very rare exomes 14/1,461,636 · genomes 2/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
Remaining individualsnot grpmax-eligible	0.0032%	31,230
East Asian	0.00223%	44,904
European (non-Finnish)	0.000848%	117,987

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: MEF2A
Protein: p.Pro331=
Coding: c.993G>A
MANE Select: NM_001319206
Type: single nucleotide variant
Location: chr15:99706839 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.90 · 10 PDB

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-pro331 (accessed [today's date]).

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