Is SUN1 p.Val122= (c.366C>T) pathogenic?

SUN1 p.Val122= (c.366C>T) is classified Benign in SUN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.87%, sas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN1 p.Val122= (c.366C>T)?

SUN1 p.Val122= (c.366C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN1 p.Val122= (c.366C>T) in the general population?

SUN1 p.Val122= (c.366C>T) is low-frequency (popmax 1.87%, sas) (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.Val122=

c.366C>T · rs41273066 · VCV461660

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.87%, sas)

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.3
Overall
CADD	0.859	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.87% South Asian · 1,706/91,084 alleles

Filtering AF 1.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.77%

Overall 1.48% 23,812/1,614,188 alleles · low-frequency exomes 22,192/1,461,882 · genomes 1,620/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.87%	53
European (non-Finnish)	1.66%	60
Remaining individualsnot grpmax-eligible	1.47%	68
Finnishnot grpmax-eligible	1.15%	87
Middle Eastern	0.858%	117
Admixed American	0.75%	133
Ashkenazi Jewishnot grpmax-eligible	0.611%	164
African / African-American	0.275%	364
Amishnot grpmax-eligible	0.11%	910
East Asian	0.00446%	22,441

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.Val122=
Coding: c.366C>T
MANE Select: NM_001130965
dbSNP: rs41273066
Type: single nucleotide variant
Location: chr7:842045 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 122: the 'lmna-binding' 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-val122 (accessed [today's date]).

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