Is SUN2 p.Ser503= (c.1509G>A) pathogenic?

SUN2 p.Ser503= (c.1509G>A) is classified Likely benign in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-18). Ultra-rare (popmax 0.0657%, mid); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Ser503= (c.1509G>A)?

SUN2 p.Ser503= (c.1509G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Ser503= (c.1509G>A) in the general population?

SUN2 p.Ser503= (c.1509G>A) is ultra-rare (popmax 0.0657%, mid) (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.Ser503=

c.1509G>A · rs767238921 · VCV1078624

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

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 -15	GERP -4.1
Overall
CADD	0.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00155% 25/1,613,512 alleles · ultra-rare exomes 22/1,461,294 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
Remaining individualsnot grpmax-eligible	0.0096%	10,413
South Asian	0.00439%	22,772
African / African-American	0.00133%	74,944
European (non-Finnish)	0.000847%	118,003

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.Ser503=
Coding: c.1509G>A
MANE Select: NM_015374
dbSNP: rs767238921
Type: single nucleotide variant
Location: chr22:38739791 (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-ser503 (accessed [today's date]).

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