Is DNM1 p.Pro423= (c.1269G>A) pathogenic?

DNM1 p.Pro423= (c.1269G>A) is classified Likely benign in DNM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). Very rare (popmax 0.00223%, eas); Associated with developmental and epileptic encephalopathy, 31A.

What condition is associated with DNM1 p.Pro423= (c.1269G>A)?

DNM1 p.Pro423= (c.1269G>A) is associated with developmental and epileptic encephalopathy, 31A (ClinVar).

How common is DNM1 p.Pro423= (c.1269G>A) in the general population?

DNM1 p.Pro423= (c.1269G>A) is very rare (popmax 0.00223%, eas) (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.Pro423=

c.1269G>A · rs1436554330 · VCV1632913

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 5.9	GERP 1.7, phastCons 1
Overall
CADD	15.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000929% 15/1,613,984 alleles · very rare exomes 14/1,461,770 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
African / African-American	0.00133%	74,924
South Asian	0.0011%	91,074
European (non-Finnish)	0.00102%	98,331

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.Pro423=
Coding: c.1269G>A
MANE Select: NM_004408
dbSNP: rs1436554330
Type: single nucleotide variant
Location: chr9:128224323 (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 423: an α-helix; 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.Pro423Leu Uncertain significance ★ ⚠ same residue
DNM1 p.Pro423Thr 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

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-pro423 (accessed [today's date]).

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