Is DNM2 p.Pro263= (c.789G>A) pathogenic?

DNM2 p.Pro263= (c.789G>A) is classified Benign/Likely benign in DNM2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Rare (popmax 0.428%, eas); Associated with Inborn genetic diseases.

What condition is associated with DNM2 p.Pro263= (c.789G>A)?

DNM2 p.Pro263= (c.789G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease dominant intermediate B (ClinVar).

How common is DNM2 p.Pro263= (c.789G>A) in the general population?

DNM2 p.Pro263= (c.789G>A) is rare (popmax 0.428%, eas) (gnomAD).

DNM2 p.Pro263=

c.789G>A · rs199976453 · VCV287974

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.428%, eas)

Conditions

Inborn genetic diseases

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 -5.4	GERP -3.7
Overall
CADD	4.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.428% East Asian · 192/44,886 alleles

Filtering AF 0.378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.359%

Overall 0.0128% 206/1,613,846 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.428%	234
Remaining individualsnot grpmax-eligible	0.0096%	10,418
African / African-American	0.004%	25,020
South Asian	0.0011%	91,092
European (non-Finnish)	0.000339%	295,010

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.Pro263=
Coding: c.789G>A
MANE Select: NM_001005361
dbSNP: rs199976453
Type: single nucleotide variant
Location: chr19:10783060 (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

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

Also linked: Charcot-Marie-Tooth disease dominant intermediate B

Similar variants

DNM2 p.Pro263Leu Benign ★★ ⚠ same residue
DNM2 p.Pro263Arg Uncertain significance ★ ⚠ same residue
DNM2 p.Pro263Gln Uncertain significance ★ ⚠ same residue
DNM2 p.Pro263Ser 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-pro263 (accessed [today's date]).

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