Is SUN1 p.Ile464Val (c.1390A>G) pathogenic?

SUN1 p.Ile464Val (c.1390A>G) is classified Conflicting classifications of pathogenicity in SUN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-03). Very rare (popmax 0.008%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Ile464Val (c.1390A>G)?

SUN1 p.Ile464Val (c.1390A>G) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Ile464Val (c.1390A>G) in the general population?

SUN1 p.Ile464Val (c.1390A>G) is very rare (popmax 0.008%, 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.Ile464Val

c.1390A>G · rs199915497 · VCV1037447

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -9.5
Regional constraint	o/e 1.09	unconstrained · MANE · 28 kb · p 0.01 · regional, not allelic
Overall
CADD	0.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.008% African / African-American · 6/75,040 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00279% 45/1,614,118 alleles · very rare exomes 39/1,461,834 · genomes 6/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,507
European (non-Finnish)	0.00305%	32,778
East Asian	0.00223%	44,878
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Ile464Val
Coding: c.1390A>G
MANE Select: NM_001130965
dbSNP: rs199915497
Type: single nucleotide variant
Location: chr7:856397 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB

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-ile464val (accessed [today's date]).

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