Is DNM3 p.Pro751Ser (c.2251C>T) pathogenic?

DNM3 p.Pro751Ser (c.2251C>T) is classified Uncertain significance in DNM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: ambiguous (0.5362); Absent from gnomAD v4.1.

How common is DNM3 p.Pro751Ser (c.2251C>T) in the general population?

DNM3 p.Pro751Ser (c.2251C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNM3 p.Pro751Ser (c.2251C>T)?

AlphaMissense predicts ambiguous (score 0.5362) — an in-silico prediction, not a clinical call.

DNM3 p.Pro751Ser

c.2251C>T · rs2526522173 · VCV3084777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5362 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5362	ambiguous
REVEL	0.688	pathogenic-leaning
SaProt	LLR -10.63	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 99 kb · p 0.0016 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P757S vs ClinVar P751S) — 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.Pro751Ser
Coding: c.2251C>T
MANE Select: NM_015569
dbSNP: rs2526522173
Type: single nucleotide variant
Location: chr1:172387325 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 757 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-pro751ser (accessed [today's date]).

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