Is SUN2 p.Arg693Trp (c.2077C>T) pathogenic?

SUN2 p.Arg693Trp (c.2077C>T) is classified Uncertain significance in SUN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-13). AlphaMissense: ambiguous (0.5254); Very rare (popmax 0.00446%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg693Trp (c.2077C>T)?

SUN2 p.Arg693Trp (c.2077C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Arg693Trp (c.2077C>T) in the general population?

SUN2 p.Arg693Trp (c.2077C>T) is very rare (popmax 0.00446%, 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.

What do computational predictors say about SUN2 p.Arg693Trp (c.2077C>T)?

AlphaMissense predicts ambiguous (score 0.5254) — an in-silico prediction, not a clinical call.

SUN2 p.Arg693Trp

c.2077C>T · rs370298150 · VCV2600502

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Emery-Dreifuss muscular dystrophy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.5254	ambiguous
REVEL	0.478	indeterminate
SaProt	LLR -13.13	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.3	GERP 1.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,960 bp · p 0.7 · regional, not allelic
Overall
CADD	26.8	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 0.00446% East Asian · 2/44,870 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00136% 22/1,613,942 alleles · very rare exomes 22/1,461,616 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,435
Remaining individualsnot grpmax-eligible	0.0032%	31,246
African / African-American	0.00266%	37,528
European (non-Finnish)	0.00136%	73,743

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.Arg693Trp
Coding: c.2077C>T
MANE Select: NM_015374
dbSNP: rs370298150
Type: single nucleotide variant
Location: chr22:38736344 (GRCh38)

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)

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-arg693trp (accessed [today's date]).

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