Is DNM1 p.Ala808Val (c.2423C>T) pathogenic?

DNM1 p.Ala808Val (c.2423C>T) is classified Uncertain significance in DNM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-27). AlphaMissense: likely benign (0.0885); Very rare (popmax 0.000672%, nfe); Associated with developmental and epileptic encephalopathy, 31A.

What condition is associated with DNM1 p.Ala808Val (c.2423C>T)?

DNM1 p.Ala808Val (c.2423C>T) is associated with developmental and epileptic encephalopathy, 31A (ClinVar).

How common is DNM1 p.Ala808Val (c.2423C>T) in the general population?

DNM1 p.Ala808Val (c.2423C>T) is very rare (popmax 0.000672%, nfe) (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.Ala808Val (c.2423C>T)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

DNM1 p.Ala808Val

c.2423C>T · rs1474835177 · VCV933859

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000672%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 31A

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 806 bp · p 1.8e-10 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000672% European (non-Finnish) · 7/1,040,894 alleles

Filtering AF 0.00028% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00018%

Overall 0.000533% 7/1,313,778 alleles · very rare exomes 5/1,161,830 · genomes 2/151,948 · joint denominator

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.Ala808Val
Coding: c.2423C>T
MANE Select: NM_004408
dbSNP: rs1474835177
Type: single nucleotide variant
Location: chr9:128250829 (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 808: a UniProt-annotated variant site (in dee31b); the 'disordered' 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 p.Ala808Thr 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-ala808val (accessed [today's date]).

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