Is SUN2 p.Ser22del (c.55AGC[3]) pathogenic?

SUN2 p.Ser22del (c.55AGC[3]) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). Ultra-rare (popmax 0.0333%, amr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Ser22del (c.55AGC[3])?

SUN2 p.Ser22del (c.55AGC[3]) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Ser22del (c.55AGC[3]) in the general population?

SUN2 p.Ser22del (c.55AGC[3]) is ultra-rare (popmax 0.0333%, amr) (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.Ser22del

c.55AGC[3] · rs781129819 · VCV1502542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

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 7.5	GERP 2.1, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% Admixed American · 20/60,022 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00124% 20/1,613,848 alleles · ultra-rare exomes 20/1,461,474 · genomes 0/152,374 · 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: SUN2
Protein: p.Ser22del
Coding: c.55AGC[3]
MANE Select: NM_015374
dbSNP: rs781129819
Type: Microsatellite
Location: chr22:38752563 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB
Residue 22: the 'lmna-binding' region; the 'disordered' 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.Ser22= Likely benign ★ same residue
SUN2 p.Arg105del 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-ser22del (accessed [today's date]).

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