Is SUN2 p.Ala380Asp (c.1139C>A) pathogenic?

SUN2 p.Ala380Asp (c.1139C>A) is classified Uncertain significance in SUN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-13). AlphaMissense: likely benign (0.1815); Ultra-rare (popmax 0.0494%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Ala380Asp (c.1139C>A)?

SUN2 p.Ala380Asp (c.1139C>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Ala380Asp (c.1139C>A) in the general population?

SUN2 p.Ala380Asp (c.1139C>A) is ultra-rare (popmax 0.0494%, 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.

What do computational predictors say about SUN2 p.Ala380Asp (c.1139C>A)?

AlphaMissense predicts likely benign (score 0.1815) — an in-silico prediction, not a clinical call.

SUN2 p.Ala380Asp

c.1139C>A · rs143302352 · VCV648637

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Emery-Dreifuss muscular dystrophy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1815	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% African / African-American · 37/74,934 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00248% 40/1,613,794 alleles · ultra-rare exomes 17/1,461,562 · genomes 23/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0494%	2,025
Admixed American	0.005%	20,003

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.Ala380Asp
Coding: c.1139C>A
MANE Select: NM_015374
dbSNP: rs143302352
Type: single nucleotide variant
Location: chr22:38741501 (GRCh38)

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)

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-ala380asp (accessed [today's date]).

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