Is SUN1 p.Ser209fs (c.624_625insGGGTGCTCAC…[38 bp]) pathogenic?

SUN1 p.Ser209fs (c.624625insGGGTGCTCAC…[38 bp]) is classified Uncertain significance in SUN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-12). Absent from gnomAD; Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Ser209fs (c.624_625insGGGTGCTCAC…[38 bp])?

SUN1 p.Ser209fs (c.624_625insGGGTGCTCAC…[38 bp]) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Ser209fs (c.624_625insGGGTGCTCAC…[38 bp]) in the general population?

SUN1 p.Ser209fs (c.624_625insGGGTGCTCAC…[38 bp]) is absent from gnomAD (gnomAD).

How is Emery-Dreifuss muscular dystrophy inherited?

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

SUN1 p.Ser209fs

c.624_625insGGGTGCTCAC…[38 bp] · rs2486406165 · VCV2121691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.3	GERP -2.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SUN1
Protein: p.Ser209fs
Coding: c.624_625insGGGTGCTCACGGCGCACCCCGCGGCCCCCGGGCCCGTG
MANE Select: NM_001130965
dbSNP: rs2486406165
Type: Insertion
Location: chr7:843450 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 209: the 'syne2-binding' region

Full SUN1 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

SUN1 p.Ser209= Likely benign ★ same residue
SUN1 p.Ser209Leu Uncertain significance ★ same residue
SUN1 c.452-13_452-12insG Likely benign ★ same condition
SUN1 p.Ala179Thr Uncertain significance ★★ same condition
SUN1 p.Ala203Thr Uncertain significance ★★ same condition
SUN1 p.Ala232Val Uncertain significance ★★ same condition
SUN1 p.Ala236Thr Uncertain significance ★★ same condition
SUN1 p.Ala255Thr 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/sun1-p-ser209fs (accessed [today's date]).

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