Is SUN1 p.Arg681= (c.2043G>A) pathogenic?

SUN1 p.Arg681= (c.2043G>A) is classified Benign in SUN1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-30). Common (popmax 15%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Arg681= (c.2043G>A)?

SUN1 p.Arg681= (c.2043G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How is Emery-Dreifuss muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SUN1 p.Arg681=

Q: How common is SUN1 p.Arg681= (c.2043G>A) in the general population?

SUN1 p.Arg681= (c.2043G>A) is common (popmax 15%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2043G>A · rs61744747 · VCV461646

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 15%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 2.3, phastCons 1
Overall
CADD	7.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15% East Asian · 6,749/44,844 alleles

Filtering AF 14.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 1.35% 21,797/1,613,780 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	15%	7
Middle Eastern	3.19%	31
Finnishnot grpmax-eligible	2.81%	36
South Asian	2.76%	36
Ashkenazi Jewishnot grpmax-eligible	1.76%	57
Remaining individualsnot grpmax-eligible	1.69%	59
European (non-Finnish)	0.73%	137
Admixed American	0.357%	280
African / African-American	0.173%	577

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: SUN1
Protein: p.Arg681=
Coding: c.2043G>A
MANE Select: NM_001130965
dbSNP: rs61744747
Type: single nucleotide variant
Location: chr7:869411 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 681: the sun domain; a β-strand; the 'sufficient for interaction with syne1 and syne2' region

Full SUN1 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

SUN1 p.Ala179Thr Uncertain significance ★★ same condition
SUN1 p.Ala203Thr Uncertain significance ★★ same condition
SUN1 p.Ala232Val Uncertain significance ★★ same condition
SUN1 p.Ala236Thr Uncertain significance ★★ same condition
SUN1 p.Ala255Thr Uncertain significance ★★ same condition
SUN1 p.Ala256Val Uncertain significance ★★ same condition
SUN1 p.Ala404Thr Uncertain significance ★★ same condition
SUN1 p.Ala414Thr 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/sun1-p-arg681 (accessed [today's date]).

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