Is DNM3 p.Pro765Ala (c.2293C>G) pathogenic?

DNM3 p.Pro765Ala (c.2293C>G) is classified Uncertain significance in DNM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: likely benign (0.062); Absent from gnomAD v4.1.

How common is DNM3 p.Pro765Ala (c.2293C>G) in the general population?

DNM3 p.Pro765Ala (c.2293C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNM3 p.Pro765Ala (c.2293C>G)?

AlphaMissense predicts likely benign (score 0.062) — an in-silico prediction, not a clinical call.

DNM3 p.Pro765Ala

c.2293C>G · VCV3841701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.062 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.062	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 99 kb · p 0.0016 · regional, not allelic
Overall
CADD	22.9	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P771A vs ClinVar P765A) — verify the residue.

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: DNM3
Protein: p.Pro765Ala
Coding: c.2293C>G
MANE Select: NM_015569
Type: single nucleotide variant
Location: chr1:172388580 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 771 UniProt numbering: the 'disordered' region

Full DNM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNM3 p.Arg290Gln Uncertain significance ★★ ⚠ same type
DNM3 p.Asn686= Benign ★★ same type
DNM3 p.Thr833= Benign ★★ same type
DNM3 p.Ala19Val Uncertain significance ★ same type
DNM3 p.Ala254Ser Uncertain significance ★ ⚠ same type
DNM3 p.Ala254Thr Uncertain significance ★ ⚠ same type
DNM3 p.Ala313Thr Uncertain significance ★ ⚠ same type
DNM3 p.Ala337Ser Uncertain significance ★ ⚠ 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/dnm3-p-pro765ala (accessed [today's date]).

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