Is SUN2 p.Trp182Arg (c.544T>C) pathogenic?

SUN2 p.Trp182Arg (c.544T>C) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely pathogenic (0.6033); Very rare (popmax 0.00439%, sas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Trp182Arg (c.544T>C)?

SUN2 p.Trp182Arg (c.544T>C) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Trp182Arg (c.544T>C) in the general population?

SUN2 p.Trp182Arg (c.544T>C) is very rare (popmax 0.00439%, 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.

What do computational predictors say about SUN2 p.Trp182Arg (c.544T>C)?

AlphaMissense predicts likely pathogenic (score 0.6033) — an in-silico prediction, not a clinical call.

SUN2 p.Trp182Arg

c.544T>C · VCV3620524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6033 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.6033	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,056 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00118% 19/1,613,742 alleles · very rare exomes 16/1,461,588 · genomes 3/152,154 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,764
European (non-Finnish)	0.00127%	78,664

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: SUN2
Protein: p.Trp182Arg
Coding: c.544T>C
MANE Select: NM_015374
Type: single nucleotide variant
Location: chr22:38749836 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB

Full SUN2 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

SUN2 p.Ala158Thr Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala251Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala508Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala56Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg100Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Trp Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg104Lys 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/sun2-p-trp182arg (accessed [today's date]).

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