Is SUN1 p.Asn705Ser (c.2114A>G) pathogenic?

SUN1 p.Asn705Ser (c.2114A>G) is classified Benign in SUN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.68%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Asn705Ser (c.2114A>G)?

SUN1 p.Asn705Ser (c.2114A>G) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Asn705Ser (c.2114A>G) in the general population?

SUN1 p.Asn705Ser (c.2114A>G) is low-frequency (popmax 1.68%, 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.

SUN1 p.Asn705Ser

c.2114A>G · rs138051124 · VCV461648

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.68%, afr)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.169	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 4.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 13 kb · p 0.0008 · regional, not allelic
Overall
CADD	19.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.68% African / African-American · 1,258/75,006 alleles

Filtering AF 1.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.57%

Overall 0.0886% 1,430/1,613,806 alleles · low-frequency exomes 663/1,461,562 · genomes 767/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.68%	60
Remaining individualsnot grpmax-eligible	0.107%	933
Admixed American	0.09%	1,111
Middle Eastern	0.0498%	2,009
South Asian	0.00439%	22,767
European (non-Finnish)	0.00373%	26,814

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.Asn705Ser
Coding: c.2114A>G
MANE Select: NM_001130965
dbSNP: rs138051124
Type: single nucleotide variant
Location: chr7:869482 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 705: the sun domain; 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.Asn705= Likely benign ★ same residue
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

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-asn705ser (accessed [today's date]).

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