Is DNM2 p.Pro319= (c.957C>T) pathogenic?

DNM2 p.Pro319= (c.957C>T) is classified Likely benign in DNM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-26). Ultra-rare (popmax 0.0317%, amr); Associated with Charcot-Marie-Tooth disease dominant intermediate B.

What condition is associated with DNM2 p.Pro319= (c.957C>T)?

DNM2 p.Pro319= (c.957C>T) is associated with Charcot-Marie-Tooth disease dominant intermediate B (ClinVar).

How common is DNM2 p.Pro319= (c.957C>T) in the general population?

DNM2 p.Pro319= (c.957C>T) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

DNM2 p.Pro319=

Q: How is Autosomal dominant intermediate Charcot-Marie-Tooth disease type B inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.957C>T · rs141911457 · VCV510490

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Conditions

Charcot-Marie-Tooth disease dominant intermediate B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.7
Overall
CADD	2.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0317% Admixed American · 19/60,010 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00502% 81/1,614,102 alleles · ultra-rare exomes 60/1,461,874 · genomes 21/152,228 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,158
East Asian	0.0134%	7,480
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.00398%	25,107
Finnishnot grpmax-eligible	0.00312%	32,017

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: DNM2
Protein: p.Pro319=
Coding: c.957C>T
MANE Select: NM_001005361
dbSNP: rs141911457
Type: single nucleotide variant
Location: chr19:10786671 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 1 PDB

Full DNM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease dominant intermediate B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant intermediate Charcot-Marie-Tooth disease type B (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

DNM2 p.Pro319Ala Uncertain significance ★ ⚠ same residue
DNM2 p.Pro319Leu Uncertain significance ★ ⚠ same residue
DNM2 p.Ala618Thr Pathogenic ★★★ same condition
DNM2 p.Arg369Gln Pathogenic ★★★ ⚠ same condition
DNM2 p.Arg369Trp Pathogenic ★★★ same condition
DNM2 p.Arg465Trp Pathogenic ★★★ same condition
DNM2 p.Arg522Cys Likely pathogenic ★★★ same condition
DNM2 p.Arg522His 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/dnm2-p-pro319 (accessed [today's date]).

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