Is DNM1 p.Ser751Arg (c.2251A>C) pathogenic?

DNM1 p.Ser751Arg (c.2251A>C) is classified Uncertain significance in DNM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-30). AlphaMissense: likely pathogenic (0.9819); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 31A.

What condition is associated with DNM1 p.Ser751Arg (c.2251A>C)?

DNM1 p.Ser751Arg (c.2251A>C) is associated with developmental and epileptic encephalopathy, 31A (ClinVar).

How common is DNM1 p.Ser751Arg (c.2251A>C) in the general population?

DNM1 p.Ser751Arg (c.2251A>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.Ser751Arg (c.2251A>C)?

AlphaMissense predicts likely pathogenic (score 0.9819) — an in-silico prediction, not a clinical call.

DNM1 p.Ser751Arg

c.2251A>C · rs2539123405 · VCV2850971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9819 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

developmental and epileptic encephalopathy, 31A

Computational evidence

Protein change
AlphaMissense	0.9819	likely pathogenic
REVEL	0.564	indeterminate
SaProt	LLR -11.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.1	GERP 2, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 806 bp · p 1.8e-10 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Ser751Arg
Coding: c.2251A>C
MANE Select: NM_004408
dbSNP: rs2539123405
Type: single nucleotide variant
Location: chr9:128250289 (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 751: 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 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-ser751arg (accessed [today's date]).

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