Is SUN2 p.His242= (c.726C>T) pathogenic?

SUN2 p.His242= (c.726C>T) is classified Likely benign in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-09). Ultra-rare (popmax 0.0495%, mid); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.His242= (c.726C>T)?

SUN2 p.His242= (c.726C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.His242= (c.726C>T) in the general population?

SUN2 p.His242= (c.726C>T) is ultra-rare (popmax 0.0495%, 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.His242=

c.726C>T · rs539723941 · VCV705836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.025	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -4, phastCons 0.14
Overall
CADD	6.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00235% 38/1,614,118 alleles · ultra-rare exomes 30/1,461,778 · genomes 8/152,340 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
African / African-American	0.032%	3,127
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.0022%	45,541
European (non-Finnish)	0.000169%	590,009

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.His242=
Coding: c.726C>T
MANE Select: NM_015374
dbSNP: rs539723941
Type: single nucleotide variant
Location: chr22:38745771 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB

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)

Similar variants

SUN2 p.His242Tyr Uncertain significance ★ ⚠ same residue
SUN2 p.Ala158Thr Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala251Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala508Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala56Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg100Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Trp 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/sun2-p-his242 (accessed [today's date]).

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