Is SUN2 p.Asp92= (c.276C>T) pathogenic?

SUN2 p.Asp92= (c.276C>T) is classified Benign in SUN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.233%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Asp92= (c.276C>T)?

SUN2 p.Asp92= (c.276C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Asp92= (c.276C>T) in the general population?

SUN2 p.Asp92= (c.276C>T) is rare (popmax 0.233%, 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.Asp92=

c.276C>T · rs111670814 · VCV461684

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.233%, afr)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.47	GERP -4.3
Overall
CADD	4.422	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.233% African / African-American · 175/75,032 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.0187% 302/1,612,412 alleles · rare exomes 200/1,460,074 · genomes 102/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.233%	429
Remaining individualsnot grpmax-eligible	0.0497%	2,014
East Asian	0.0401%	2,491
Admixed American	0.0317%	3,153
South Asian	0.0187%	5,356
Middle Eastern	0.0165%	6,052
European (non-Finnish)	0.00339%	29,466
Finnishnot grpmax-eligible	0.00156%	64,010

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.Asp92=
Coding: c.276C>T
MANE Select: NM_015374
dbSNP: rs111670814
Type: single nucleotide variant
Location: chr22:38751220 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB
Residue 92: the 'lmna-binding' region

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.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
SUN2 p.Arg104Lys 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-asp92 (accessed [today's date]).

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