Is SUN1 p.Phe644fs (c.1932del) pathogenic?

SUN1 p.Phe644fs (c.1932del) is classified Uncertain significance in SUN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-19). Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Phe644fs (c.1932del)?

SUN1 p.Phe644fs (c.1932del) 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.

SUN1 p.Phe644fs

c.1932del · VCV3727173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: SUN1
Protein: p.Phe644fs
Coding: c.1932del
MANE Select: NM_001130965
Type: Deletion
Location: chr7:866017 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 644: the sun domain; the 'sufficient for interaction with syne1 and syne2' 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 c.452-3del Benign ★★ same condition
SUN1 c.1220_1263+16del Uncertain significance ★ same condition
SUN1 p.Gln675fs Uncertain significance ★ same condition
SUN1 p.Ile226fs Uncertain significance ★ same condition
SUN1 c.1053+17del Likely benign ★ same condition
SUN1 c.1394+20_1394+21del Likely benign ★ same condition
SUN1 c.2242-14del Benign ★ same condition
SUN1 c.267-6del Likely benign ★ 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-phe644fs (accessed [today's date]).

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