Is DNM1 p.Lys89Asn (c.267G>T) pathogenic?

DNM1 p.Lys89Asn (c.267G>T) is classified Uncertain significance in DNM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-27). AlphaMissense: likely pathogenic (0.9474); Very rare (popmax 0.00267%, afr); Associated with developmental and epileptic encephalopathy, 31A.

What condition is associated with DNM1 p.Lys89Asn (c.267G>T)?

DNM1 p.Lys89Asn (c.267G>T) is associated with developmental and epileptic encephalopathy, 31A (ClinVar).

How common is DNM1 p.Lys89Asn (c.267G>T) in the general population?

DNM1 p.Lys89Asn (c.267G>T) is very rare (popmax 0.00267%, afr) (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.Lys89Asn (c.267G>T)?

AlphaMissense predicts likely pathogenic (score 0.9474) — an in-silico prediction, not a clinical call.

DNM1 p.Lys89Asn

c.267G>T · rs1229779896 · VCV1412439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9474 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 31A

Computational evidence

Protein change
AlphaMissense	0.9474	likely pathogenic
REVEL	0.725	pathogenic-leaning
SaProt	LLR -13.79	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 6.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 17 kb · p 4.8e-19 · regional, not allelic
Overall
CADD	29.0	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

Grpmax group 0.00267% African / African-American · 2/74,872 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,613,468 alleles · very rare exomes 3/1,461,396 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,436
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	8.48e-05%	1,179,638

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.Lys89Asn
Coding: c.267G>T
MANE Select: NM_004408
dbSNP: rs1229779896
Type: single nucleotide variant
Location: chr9:128218613 (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 89: the dynamin-type g domain; 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.Lys89Glu 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-lys89asn (accessed [today's date]).

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