Is SUN2 p.Arg307Cys (c.919C>T) pathogenic?

SUN2 p.Arg307Cys (c.919C>T) is classified Uncertain significance in SUN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-09). AlphaMissense: likely benign (0.2233); Ultra-rare (popmax 0.0936%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg307Cys (c.919C>T)?

SUN2 p.Arg307Cys (c.919C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Arg307Cys (c.919C>T) in the general population?

SUN2 p.Arg307Cys (c.919C>T) is ultra-rare (popmax 0.0936%, 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.Arg307Cys (c.919C>T)?

AlphaMissense predicts likely benign (score 0.2233) — an in-silico prediction, not a clinical call.

SUN2 p.Arg307Cys

c.919C>T · rs758857415 · VCV1520715

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2233 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0936%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

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	0.2233	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -12.57	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	24.5	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 0.0936% East Asian · 42/44,894 alleles

Filtering AF 0.0711% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0632%

Overall 0.00372% 60/1,613,486 alleles · ultra-rare exomes 52/1,461,264 · genomes 8/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0936%	1,069
African / African-American	0.00667%	14,989
Admixed American	0.005%	20,002
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Finnishnot grpmax-eligible	0.00158%	63,452
South Asian	0.0011%	91,092
European (non-Finnish)	0.000424%	236,003

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.Arg307Cys
Coding: c.919C>T
MANE Select: NM_015374
dbSNP: rs758857415
Type: single nucleotide variant
Location: chr22:38742450 (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-arg307cys (accessed [today's date]).

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