Is SUN1 p.Ala466= (c.1398G>A) pathogenic?

SUN1 p.Ala466= (c.1398G>A) is classified Likely benign in SUN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-04). Rare (popmax 0.337%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Ala466= (c.1398G>A)?

SUN1 p.Ala466= (c.1398G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Ala466= (c.1398G>A) in the general population?

SUN1 p.Ala466= (c.1398G>A) is rare (popmax 0.337%, eas) (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.Ala466=

c.1398G>A · rs752157539 · VCV706074

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.337%, eas)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	Δ0.88	acceptor gain · deltas
Pangolin	Δ0.33	gain · loss 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -3	GERP -5.1
Overall
CADD	18.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.337% East Asian · 148/43,918 alleles

Filtering AF 0.293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.276%

Overall 0.0137% 216/1,578,944 alleles · rare exomes 195/1,426,632 · genomes 21/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.337%	297
African / African-American	0.0203%	4,937
Middle Eastern	0.0169%	5,930
Remaining individualsnot grpmax-eligible	0.00987%	10,134
European (non-Finnish)	0.0038%	26,282
Admixed American	0.00178%	56,252
Finnishnot grpmax-eligible	0.00157%	63,528

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.Ala466=
Coding: c.1398G>A
MANE Select: NM_001130965
dbSNP: rs752157539
Type: single nucleotide variant
Location: chr7:857831 (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-ala466 (accessed [today's date]).

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