Is SUN1 p.Ala587Val (c.1760C>T) pathogenic?

SUN1 p.Ala587Val (c.1760C>T) is classified Likely benign in SUN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Rare (popmax 0.633%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Ala587Val (c.1760C>T)?

SUN1 p.Ala587Val (c.1760C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Ala587Val (c.1760C>T) in the general population?

SUN1 p.Ala587Val (c.1760C>T) is rare (popmax 0.633%, 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.Ala587Val

c.1760C>T · rs114701323 · VCV530830

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.633%, afr)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.092	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP 3.2, phastCons 0.006
Regional constraint	o/e 1.09	unconstrained · MANE · 28 kb · p 0.01 · regional, not allelic
Overall
CADD	7.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.633% African / African-American · 475/75,044 alleles

Filtering AF 0.586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.567%

Overall 0.0335% 541/1,613,742 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.633%	158
Admixed American	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Middle Eastern	0.0165%	6,044
East Asian	0.00223%	44,864
European (non-Finnish)	0.000848%	117,977

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.Ala587Val
Coding: c.1760C>T
MANE Select: NM_001130965
dbSNP: rs114701323
Type: single nucleotide variant
Location: chr7:860363 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 587: a UniProt-annotated variant site (in); 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-ala587val (accessed [today's date]).

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