Is MEF2D p.Pro330Ser (c.988C>T) pathogenic?

MEF2D p.Pro330Ser (c.988C>T) is classified Uncertain significance in MEF2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0921); Ultra-rare (popmax 0.0249%, nfe).

How common is MEF2D p.Pro330Ser (c.988C>T) in the general population?

MEF2D p.Pro330Ser (c.988C>T) is ultra-rare (popmax 0.0249%, nfe) (gnomAD).

What do computational predictors say about MEF2D p.Pro330Ser (c.988C>T)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

MEF2D p.Pro330Ser

c.988C>T · rs199562852 · VCV2456570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0249%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -5.75	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 12	GERP 2.2, 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

Grpmax group 0.0249% European (non-Finnish) · 294/1,180,024 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0217%

Overall 0.0193% 311/1,614,084 alleles · ultra-rare exomes 292/1,461,838 · genomes 19/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0249%	4,014
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00934%	10,707
Admixed American	0.00333%	30,008
Finnishnot grpmax-eligible	0.00156%	64,034

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: MEF2D
Protein: p.Pro330Ser
Coding: c.988C>T
MANE Select: NM_005920
dbSNP: rs199562852
Type: single nucleotide variant
Location: chr1:156475126 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.81 · 2 PDB

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

Similar variants

MEF2D p.Ala200Pro Uncertain significance ★ ⚠ same type
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

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-pro330ser (accessed [today's date]).

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