Is SUN1 p.Phe713= (c.2139C>T) pathogenic?

SUN1 p.Phe713= (c.2139C>T) is classified Likely benign in SUN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). Very rare (popmax 0.00891%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Phe713= (c.2139C>T)?

SUN1 p.Phe713= (c.2139C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Phe713= (c.2139C>T) in the general population?

SUN1 p.Phe713= (c.2139C>T) is very rare (popmax 0.00891%, 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.Phe713=

c.2139C>T · rs777094056 · VCV1077352

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.442	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.7	GERP -4.8
Overall
CADD	1.408	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00118% 19/1,613,354 alleles · very rare exomes 18/1,461,194 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
African / African-American	0.00401%	24,965
Remaining individualsnot grpmax-eligible	0.0016%	62,442
European (non-Finnish)	0.000932%	107,250

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.Phe713=
Coding: c.2139C>T
MANE Select: NM_001130965
dbSNP: rs777094056
Type: single nucleotide variant
Location: chr7:869507 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 713: the sun domain; a β-strand; 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 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
SUN1 p.Ala414Thr 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-phe713 (accessed [today's date]).

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