Is SUN2 p.Leu511= (c.1533G>C) pathogenic?

SUN2 p.Leu511= (c.1533G>C) is classified Likely benign in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Rare (popmax 0.238%, sas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Leu511= (c.1533G>C)?

SUN2 p.Leu511= (c.1533G>C) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Leu511= (c.1533G>C) in the general population?

SUN2 p.Leu511= (c.1533G>C) is rare (popmax 0.238%, sas) (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.Leu511=

c.1533G>C · rs528608235 · VCV1157461

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.238%, sas)

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 0.41	GERP -0.19, phastCons 0.97
Overall
CADD	2.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.238% South Asian · 217/91,082 alleles

Filtering AF 0.212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.202%

Overall 0.0139% 225/1,613,690 alleles · rare exomes 215/1,461,350 · genomes 10/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.238%	420
Remaining individualsnot grpmax-eligible	0.0128%	7,812

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.Leu511=
Coding: c.1533G>C
MANE Select: NM_015374
dbSNP: rs528608235
Type: single nucleotide variant
Location: chr22:38739767 (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-leu511 (accessed [today's date]).

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