Is DNM1 p.Pro450= (c.1350G>A) pathogenic?

DNM1 p.Pro450= (c.1350G>A) is classified Likely benign in DNM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-06). Very rare (popmax 0.0092%, amr); Associated with developmental and epileptic encephalopathy, 31A.

What condition is associated with DNM1 p.Pro450= (c.1350G>A)?

DNM1 p.Pro450= (c.1350G>A) is associated with developmental and epileptic encephalopathy, 31A (ClinVar).

How common is DNM1 p.Pro450= (c.1350G>A) in the general population?

DNM1 p.Pro450= (c.1350G>A) is very rare (popmax 0.0092%, amr) (gnomAD).

How is Lennox-Gastaut syndrome inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

DNM1 p.Pro450=

c.1350G>A · VCV3706139

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0092%, amr)

Conditions

developmental and epileptic encephalopathy, 31A

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 -7.3	GERP -7.4
Overall
CADD	1.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0092% Admixed American · 5/54,374 alleles

Filtering AF 0.00353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00235%

Overall 0.00102% 16/1,571,500 alleles · very rare exomes 13/1,419,348 · genomes 3/152,152 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0092%	10,875
East Asian	0.00238%	42,094
South Asian	0.00235%	42,605
Remaining individualsnot grpmax-eligible	0.00164%	60,846
European (non-Finnish)	0.000604%	165,591

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: DNM1
Protein: p.Pro450=
Coding: c.1350G>A
MANE Select: NM_004408
Type: single nucleotide variant
Location: chr9:128234035 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.87 · 22 PDB
Residue 450: a turn; a UniProt-annotated variant site (in dee31b)

Full DNM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 31A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lennox-Gastaut syndrome (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial, Not applicable
Onset: Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

DNM1 p.Pro450Leu Uncertain significance ★ ⚠ same residue
DNM1 c.1335+1638G>A Pathogenic/Likely pathogenic ★★ same condition
DNM1 p.Arg237Trp Pathogenic ★★ same condition
DNM1 p.Arg361Gly Likely pathogenic ★★ same condition
DNM1 p.Arg399Ter Pathogenic/Likely pathogenic ★★ same condition
DNM1 p.Asp211Val Pathogenic/Likely pathogenic ★★ same condition
DNM1 p.Gln148Arg Pathogenic/Likely pathogenic ★★ same condition
DNM1 p.Gln148Lys Likely pathogenic ★★ 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/dnm1-p-pro450 (accessed [today's date]).

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