Is SUN2 p.Arg304Gln (c.911G>A) pathogenic?

SUN2 p.Arg304Gln (c.911G>A) is classified Uncertain significance in SUN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-30). AlphaMissense: likely benign (0.1015); Very rare (popmax 0.00667%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg304Gln (c.911G>A)?

SUN2 p.Arg304Gln (c.911G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Arg304Gln (c.911G>A) in the general population?

SUN2 p.Arg304Gln (c.911G>A) is very rare (popmax 0.00667%, afr) (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.Arg304Gln (c.911G>A)?

AlphaMissense predicts likely benign (score 0.1015) — an in-silico prediction, not a clinical call.

SUN2 p.Arg304Gln

c.911G>A · rs372788944 · VCV1348352

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1015 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

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	0.1015	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -10.67	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 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	26.1	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 0.00667% African / African-American · 5/74,936 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00254% 41/1,613,548 alleles · very rare exomes 37/1,461,358 · genomes 4/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,987
Remaining individualsnot grpmax-eligible	0.0064%	15,620
East Asian	0.00446%	22,442
European (non-Finnish)	0.00237%	42,144
Admixed American	0.00167%	59,992
South Asian	0.0011%	91,088

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.Arg304Gln
Coding: c.911G>A
MANE Select: NM_015374
dbSNP: rs372788944
Type: single nucleotide variant
Location: chr22:38742458 (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-arg304gln (accessed [today's date]).

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