Is SUN1 p.Arg287Ter (c.859C>T) pathogenic?

SUN1 p.Arg287Ter (c.859C>T) is classified Uncertain significance in SUN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-22). Very rare (popmax 0.00223%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Arg287Ter (c.859C>T)?

SUN1 p.Arg287Ter (c.859C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Arg287Ter (c.859C>T) in the general population?

SUN1 p.Arg287Ter (c.859C>T) is very rare (popmax 0.00223%, 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.

SUN1 p.Arg287Ter

c.859C>T · rs961930316 · VCV1015889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 19
REVEL	0.117	moderately benign-leaning
Splicing
SpliceAI	Δ0.23	acceptor loss, 7 bp away · masked 0 · deltas
Pangolin	Δ0.38	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,894 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,614,184 alleles · very rare exomes 9/1,461,886 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000508%	196,671

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: SUN1
Protein: p.Arg287Ter
Coding: c.859C>T
MANE Select: NM_001130965
dbSNP: rs961930316
Type: single nucleotide variant
Location: chr7:852616 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 287: the 'syne2-binding' region; the 'emd-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.Arg287Gln Uncertain significance ★ same residue
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
SUN1 p.Ala256Val Uncertain significance ★★ same condition
SUN1 p.Ala404Thr 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-arg287ter (accessed [today's date]).

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