Is SUN2 p.Leu89Trp (c.265_266delinsTG) pathogenic?

SUN2 p.Leu89Trp (c.265266delinsTG) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Leu89Trp (c.265_266delinsTG)?

SUN2 p.Leu89Trp (c.265_266delinsTG) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How is Emery-Dreifuss muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SUN2 p.Leu89Trp

c.265_266delinsTG · VCV3681329

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic

Variant & gene context

Gene: SUN2
Protein: p.Leu89Trp
Coding: c.265_266delinsTG
MANE Select: NM_015374
Type: Indel
Location: chr22:38751230 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB
Residue 89: a UniProt-annotated variant site (in); the 'lmna-binding' region

Full SUN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Emery-Dreifuss muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Emery-Dreifuss muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

SUN2 p.Leu89Arg Benign ★★ same residue
SUN2 c.2040+19_2040+21delinsGCGTACCTGGGCAGATGCAGGTACGGGAT Uncertain significance ★ same condition
SUN2 p.Ala158Thr Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala251Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala508Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala56Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg100Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Gln Uncertain significance ★★ ⚠ 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/sun2-p-leu89trp (accessed [today's date]).

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