Is SUN2 p.Arg105del (c.306GAG[2]) pathogenic?

SUN2 p.Arg105del (c.306GAG[2]) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-26). Ultra-rare (popmax 0.0624%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg105del (c.306GAG[2])?

SUN2 p.Arg105del (c.306GAG[2]) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Arg105del (c.306GAG[2]) in the general population?

SUN2 p.Arg105del (c.306GAG[2]) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

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.Arg105del

c.306GAG[2] · rs774003824 · VCV851745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

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 0.007	GERP -4.3, phastCons 0.95
Overall
CADD	18.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0624% East Asian · 28/44,878 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.0018% 29/1,613,510 alleles · ultra-rare exomes 27/1,461,284 · genomes 2/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,603
European (non-Finnish)	8.48e-05%	1,179,838

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: SUN2
Protein: p.Arg105del
Coding: c.306GAG[2]
MANE Select: NM_015374
dbSNP: rs774003824
Type: Microsatellite
Location: chr22:38751008 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB
Residue 105: 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.Ser22del 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
SUN2 p.Arg102Trp 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-arg105del (accessed [today's date]).

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