Is SUN2 c.1663+5G>A pathogenic?

SUN2 c.1663+5G>A is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). Very rare (popmax 0.00669%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 c.1663+5G>A?

SUN2 c.1663+5G>A is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 c.1663+5G>A in the general population?

SUN2 c.1663+5G>A is very rare (popmax 0.00669%, 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.

SUN2 c.1663+5G>A

rs373767572 · VCV3009617

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

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
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.2	GERP 1.3, phastCons 0.077
Non-coding constraint	Z 6.71	1 kb window · o/e 0.61 · regional · uncalibrated
Overall
CADD	15.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,876 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000682% 11/1,612,906 alleles · very rare exomes 11/1,460,580 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,959
South Asian	0.0011%	91,090
European (non-Finnish)	0.000593%	168,562

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
Coding: c.1663+5G>A
MANE Select: NM_015374
dbSNP: rs373767572
Type: single nucleotide variant
Location: chr22:38739337 (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-c-1663-plus-5g-a (accessed [today's date]).

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