Is DNM1 p.Pro176= (c.528C>T) pathogenic?

DNM1 p.Pro176= (c.528C>T) is classified Likely benign in DNM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-20). Very rare (popmax 0.00799%, afr); Associated with developmental and epileptic encephalopathy, 31A.

What condition is associated with DNM1 p.Pro176= (c.528C>T)?

DNM1 p.Pro176= (c.528C>T) is associated with developmental and epileptic encephalopathy, 31A (ClinVar).

How common is DNM1 p.Pro176= (c.528C>T) in the general population?

DNM1 p.Pro176= (c.528C>T) is very rare (popmax 0.00799%, afr) (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.Pro176=

c.528C>T · rs146242842 · VCV511116

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00799%, afr)

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 -8.1	GERP -8.2
Overall
CADD	5.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00799% African / African-American · 6/75,048 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00136% 22/1,614,198 alleles · very rare exomes 18/1,461,862 · genomes 4/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00799%	12,508
South Asian	0.00549%	18,216
East Asian	0.00223%	44,888
European (non-Finnish)	0.000847%	118,005

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.Pro176=
Coding: c.528C>T
MANE Select: NM_004408
dbSNP: rs146242842
Type: single nucleotide variant
Location: chr9:128219191 (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 176: the dynamin-type g domain; a UniProt-annotated variant site (in dee31b); a β-strand

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 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
DNM1 p.Gly139Val 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-pro176 (accessed [today's date]).

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