Is DNM1L p.Pro85fs (c.254del) pathogenic?

DNM1L p.Pro85fs (c.254del) is classified Likely pathogenic in DNM1L (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1.

What condition is associated with DNM1L p.Pro85fs (c.254del)?

DNM1L p.Pro85fs (c.254del) is associated with encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (ClinVar).

How common is DNM1L p.Pro85fs (c.254del) in the general population?

DNM1L p.Pro85fs (c.254del) is absent from gnomAD (gnomAD).

DNM1L p.Pro85fs

c.254del · rs2540993380 · VCV2572539

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DNM1L
Protein: p.Pro85fs
Coding: c.254del
MANE Select: NM_012062 · reported on NM_001278464
dbSNP: rs2540993380
Type: Deletion
Location: chr12:32705826 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 77.09 · 11 PDB
Residue 85: the dynamin-type g domain

Full DNM1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Encephalopathy due to mitochondrial and peroxisomal fission defect (Orphanet):

Onset: Childhood, Infancy, Neonatal

Similar variants

DNM1L p.Glu116fs Pathogenic/Likely pathogenic ★★ same condition
DNM1L c.1885-15del Benign/Likely benign ★★ same condition
DNM1L p.Glu410fs Pathogenic ★ same condition
DNM1L p.Pro85Ala Uncertain significance ★ same residue
DNM1L p.Val85Leu Uncertain significance ★ ⚠ same residue
DNM1L c.1596+2T>A Likely pathogenic ★★ same condition
DNM1L c.1674+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNM1L p.Arg403Cys 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/dnm1l-p-pro85fs (accessed [today's date]).

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