Is DNM2 p.Pro792= (c.2376C>A) pathogenic?

DNM2 p.Pro792= (c.2376C>A) is classified Likely benign in DNM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). Very rare (popmax 0.00534%, afr); Associated with Charcot-Marie-Tooth disease dominant intermediate B.

What condition is associated with DNM2 p.Pro792= (c.2376C>A)?

DNM2 p.Pro792= (c.2376C>A) is associated with Charcot-Marie-Tooth disease dominant intermediate B (ClinVar).

How common is DNM2 p.Pro792= (c.2376C>A) in the general population?

DNM2 p.Pro792= (c.2376C>A) is very rare (popmax 0.00534%, afr) (gnomAD).

DNM2 p.Pro792=

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.2376C>A · rs781478890 · VCV1597737

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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.
REVEL	0.109	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2	GERP -3
Overall
CADD	6.504	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,894 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,613,806 alleles · very rare exomes 1/1,461,712 · genomes 4/152,094 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
European (non-Finnish)	8.48e-05%	1,179,888

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.Pro792=
Coding: c.2376C>A
MANE Select: NM_001005361
dbSNP: rs781478890
Type: single nucleotide variant
Location: chr19:10830211 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 1 PDB
Residue 792: the 'disordered' region

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.Pro792Thr Likely benign ★ same residue
DNM2 p.Pro792_Leu793insTer 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-pro792 (accessed [today's date]).

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