Is DNM2 p.Pro263Arg (c.788C>G) pathogenic?

DNM2 p.Pro263Arg (c.788C>G) is classified Uncertain significance in DNM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-10). AlphaMissense: ambiguous (0.4709); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease dominant intermediate B.

What condition is associated with DNM2 p.Pro263Arg (c.788C>G)?

DNM2 p.Pro263Arg (c.788C>G) is associated with Charcot-Marie-Tooth disease dominant intermediate B (ClinVar).

How common is DNM2 p.Pro263Arg (c.788C>G) in the general population?

DNM2 p.Pro263Arg (c.788C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNM2 p.Pro263Arg (c.788C>G)?

AlphaMissense predicts ambiguous (score 0.4709) — an in-silico prediction, not a clinical call.

DNM2 p.Pro263Arg

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.788C>G · rs3745674 · VCV2124225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4709 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Charcot-Marie-Tooth disease dominant intermediate B

Computational evidence

Protein change
AlphaMissense	0.4709	ambiguous
REVEL	0.745	pathogenic-leaning
SaProt	LLR -16.04	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 68 kb · p 1.3e-18 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNM2
Protein: p.Pro263Arg
Coding: c.788C>G
MANE Select: NM_001005361
dbSNP: rs3745674
Type: single nucleotide variant
Location: chr19:10783059 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 1 PDB
Residue 263: the dynamin-type g domain; a UniProt-annotated variant site (in)

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.Pro263= Benign/Likely benign ★★ same residue
DNM2 p.Pro263Leu Benign ★★ ⚠ same residue
DNM2 p.Pro263Ser Uncertain significance ★ ⚠ same residue
DNM2 p.Pro263Gln 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

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-pro263arg (accessed [today's date]).

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