Is DNM1 p.Arg66Pro (c.197G>C) pathogenic?

DNM1 p.Arg66Pro (c.197G>C) is classified Pathogenic in DNM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 31A.

What condition is associated with DNM1 p.Arg66Pro (c.197G>C)?

DNM1 p.Arg66Pro (c.197G>C) is associated with developmental and epileptic encephalopathy, 31A (ClinVar).

How common is DNM1 p.Arg66Pro (c.197G>C) in the general population?

DNM1 p.Arg66Pro (c.197G>C) is absent from gnomAD v4.1 (gnomAD).

How is Lennox-Gastaut syndrome inherited?

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

What do computational predictors say about DNM1 p.Arg66Pro (c.197G>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

DNM1 p.Arg66Pro

c.197G>C · rs2538974505 · VCV2755885

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 31A

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic ✓ concordant with ClinVar · top 3% in DNM1
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -14.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.1, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 17 kb · p 4.8e-19 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNM1
Protein: p.Arg66Pro
Coding: c.197G>C
MANE Select: NM_004408
dbSNP: rs2538974505
Type: single nucleotide variant
Location: chr9:128218266 (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 66: the dynamin-type g domain; a UniProt-annotated variant site (in dee31b); the 'g2 motif' region

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-arg66pro (accessed [today's date]).

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