Is DNM2 p.Pro765Ser (c.2293C>T) pathogenic?

DNM2 p.Pro765Ser (c.2293C>T) is classified Uncertain significance in DNM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.0766); Very rare (popmax 0.00549%, sas).

How common is DNM2 p.Pro765Ser (c.2293C>T) in the general population?

DNM2 p.Pro765Ser (c.2293C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about DNM2 p.Pro765Ser (c.2293C>T)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

DNM2 p.Pro765Ser

c.2293C>T · VCV3342117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.558	indeterminate
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,902 bp · p 0.032 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,084 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000434% 7/1,613,850 alleles · very rare exomes 7/1,461,650 · genomes 0/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,217
European (non-Finnish)	0.00017%	589,918

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.Pro765Ser
Coding: c.2293C>T
MANE Select: NM_001005361
Type: single nucleotide variant
Location: chr19:10830128 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 1 PDB
Residue 765: the 'disordered' region

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

Similar variants

DNM2 p.Pro765= Likely benign ★★ same residue
DNM2 p.Ala618Thr Pathogenic ★★★ same type
DNM2 p.Arg369Gln Pathogenic ★★★ ⚠ same type
DNM2 p.Arg369Trp Pathogenic ★★★ same type
DNM2 p.Arg465Trp Pathogenic ★★★ same type
DNM2 p.Arg522Cys Likely pathogenic ★★★ same type
DNM2 p.Arg522His Pathogenic ★★★ same type
DNM2 p.Arg523Gly Likely pathogenic ★★★ same type

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-pro765ser (accessed [today's date]).

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