Is DNM3 p.Lys89Arg (c.266A>G) pathogenic?

DNM3 p.Lys89Arg (c.266A>G) is classified Uncertain significance in DNM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.0675); Very rare (popmax 0.000256%, nfe).

How common is DNM3 p.Lys89Arg (c.266A>G) in the general population?

DNM3 p.Lys89Arg (c.266A>G) is very rare (popmax 0.000256%, nfe) (gnomAD).

What do computational predictors say about DNM3 p.Lys89Arg (c.266A>G)?

AlphaMissense predicts likely benign (score 0.0675) — an in-silico prediction, not a clinical call.

DNM3 p.Lys89Arg

c.266A>G · rs1345200287 · VCV2247010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0675	likely benign
REVEL	0.339	indeterminate
SaProt	LLR -8.99	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 3.1	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 203 kb · p 1.5e-05 · regional, not allelic
Overall
CADD	15.68	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 0.000256% European (non-Finnish) · 3/1,171,012 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000188% 3/1,592,136 alleles · very rare exomes 2/1,439,952 · genomes 1/152,184 · joint denominator

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: DNM3
Protein: p.Lys89Arg
Coding: c.266A>G
MANE Select: NM_015569
dbSNP: rs1345200287
Type: single nucleotide variant
Location: chr1:171987686 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 89: the dynamin-type g domain

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-lys89arg (accessed [today's date]).

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