Is SUN2 p.Arg114= (c.342G>A) pathogenic?

SUN2 p.Arg114= (c.342G>A) is classified Likely benign in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-01). Very rare (popmax 0.00667%, amr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg114= (c.342G>A)?

SUN2 p.Arg114= (c.342G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Arg114= (c.342G>A) in the general population?

SUN2 p.Arg114= (c.342G>A) is very rare (popmax 0.00667%, amr) (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.Arg114=

c.342G>A · rs773389007 · VCV1626745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -4.3
Overall
CADD	2.776	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,002 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000496% 8/1,613,788 alleles · very rare exomes 6/1,461,544 · genomes 2/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00133%	74,950
European (non-Finnish)	8.47e-05%	1,180,004

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.Arg114=
Coding: c.342G>A
MANE Select: NM_015374
dbSNP: rs773389007
Type: single nucleotide variant
Location: chr22:38750980 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB
Residue 114: 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-arg114 (accessed [today's date]).

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