Is DNM1 p.Phe336= (c.1008C>T) pathogenic?

DNM1 p.Phe336= (c.1008C>T) is classified Benign in DNM1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 66.9%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with DNM1 p.Phe336= (c.1008C>T)?

DNM1 p.Phe336= (c.1008C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 31A (ClinVar).

DNM1 p.Phe336=

Q: How common is DNM1 p.Phe336= (c.1008C>T) in the general population?

DNM1 p.Phe336= (c.1008C>T) is common (popmax 66.9%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1008C>T · rs3003609 · VCV380777

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 66.9%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.6	GERP -4.5
Overall
CADD	6.981	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 66.9% Admixed American · 40,115/59,976 alleles

Filtering AF 66.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.1%

Overall 53.2% 858,414/1,613,764 alleles · common exomes 792,635/1,461,744 · genomes 65,779/152,020 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	66.9%	1
Amishnot grpmax-eligible	65.9%	2
South Asian	58.2%	2
East Asian	58.2%	2
European (non-Finnish)	54.8%	2
Finnishnot grpmax-eligible	53.9%	2
Remaining individualsnot grpmax-eligible	52.4%	2
Middle Eastern	47.8%	2
Ashkenazi Jewishnot grpmax-eligible	44%	2
African / African-American	11.4%	9

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.Phe336=
Coding: c.1008C>T
MANE Select: NM_004408
dbSNP: rs3003609
Type: single nucleotide variant
Location: chr9:128222476 (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 336: a UniProt-annotated variant site (in dee31b); an α-helix

Full DNM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 31A

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-phe336 (accessed [today's date]).

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