Is SUN1 p.Thr474= (c.1422A>G) pathogenic?

SUN1 p.Thr474= (c.1422A>G) is classified Benign in SUN1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 53.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Thr474= (c.1422A>G)?

SUN1 p.Thr474= (c.1422A>G) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

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.Thr474=

Q: How common is SUN1 p.Thr474= (c.1422A>G) in the general population?

SUN1 p.Thr474= (c.1422A>G) is common (popmax 53.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1422A>G · rs10950789 · VCV1170262

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 53.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.072	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -10
Overall
CADD	0.223	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 53.5% East Asian · 23,618/44,144 alleles

Filtering AF 52.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.7%

Overall 35.8% 570,335/1,591,402 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	53.5%	2
African / African-American	50.2%	2
Admixed American	44.7%	2
Finnishnot grpmax-eligible	41.5%	2
Remaining individualsnot grpmax-eligible	35.6%	3
South Asian	34.8%	3
European (non-Finnish)	33.8%	3
Ashkenazi Jewishnot grpmax-eligible	29.2%	3
Middle Eastern	27.9%	4
Amishnot grpmax-eligible	21.5%	5

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.Thr474=
Coding: c.1422A>G
MANE Select: NM_001130965
dbSNP: rs10950789
Type: single nucleotide variant
Location: chr7:857855 (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.Thr474Pro Uncertain significance ★★ same residue
SUN1 p.Thr474Ala Uncertain significance ★ same residue
SUN1 p.Thr474Met Uncertain significance ★ 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

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-thr474 (accessed [today's date]).

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