Is SUN2 p.Asp452= (c.1356C>T) pathogenic?

SUN2 p.Asp452= (c.1356C>T) is classified Benign in SUN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.48%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Asp452= (c.1356C>T)?

SUN2 p.Asp452= (c.1356C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Asp452= (c.1356C>T) in the general population?

SUN2 p.Asp452= (c.1356C>T) is low-frequency (popmax 3.48%, afr) (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.Asp452=

c.1356C>T · rs138079219 · VCV461675

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.48%, afr)

Conditions

Emery-Dreifuss muscular dystrophy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4.6	GERP -4.1
Overall
CADD	0.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.48% African / African-American · 2,576/74,090 alleles

Filtering AF 3.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.32%

Overall 0.179% 2,810/1,573,900 alleles · low-frequency exomes 1,363/1,421,614 · genomes 1,447/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.48%	29
Remaining individualsnot grpmax-eligible	0.213%	469
Admixed American	0.122%	822
Middle Eastern	0.112%	893
South Asian	0.00814%	12,289
European (non-Finnish)	0.00216%	46,352

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.Asp452=
Coding: c.1356C>T
MANE Select: NM_015374
dbSNP: rs138079219
Type: single nucleotide variant
Location: chr22:38740267 (GRCh38)

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)

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-asp452 (accessed [today's date]).

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