Is SUN2 p.Arg348Cys (c.1042C>T) pathogenic?

SUN2 p.Arg348Cys (c.1042C>T) is classified Benign in SUN2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1474); Common (popmax 12.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg348Cys (c.1042C>T)?

SUN2 p.Arg348Cys (c.1042C>T) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

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.Arg348Cys (c.1042C>T)?

AlphaMissense predicts likely benign (score 0.1474) — an in-silico prediction, not a clinical call.

SUN2 p.Arg348Cys

Q: How common is SUN2 p.Arg348Cys (c.1042C>T) in the general population?

SUN2 p.Arg348Cys (c.1042C>T) is common (popmax 12.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1042C>T · rs138708 · VCV461670

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1474 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12.7%, eas) — too common for a highly-penetrant pathogenic allele

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	0.1474	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -11.35	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 9.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	28.5	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 12.7% East Asian · 5,663/44,580 alleles

Filtering AF 12.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.3%

Overall 2.16% 34,610/1,605,716 alleles · common exomes 32,007/1,453,484 · genomes 2,603/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	12.7%	8
Middle Eastern	2.55%	39
Ashkenazi Jewishnot grpmax-eligible	2.4%	42
Remaining individualsnot grpmax-eligible	2.17%	46
European (non-Finnish)	2.05%	49
South Asian	1.34%	75
Admixed American	1.03%	97
Finnishnot grpmax-eligible	0.657%	152
African / African-American	0.602%	166
Amishnot grpmax-eligible	0.219%	456

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.Arg348Cys
Coding: c.1042C>T
MANE Select: NM_015374
dbSNP: rs138708
Type: single nucleotide variant
Location: chr22:38742327 (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-arg348cys (accessed [today's date]).

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