Is SUN2 p.Asp668Asn (c.2002G>A) pathogenic?

SUN2 p.Asp668Asn (c.2002G>A) is classified Uncertain significance in SUN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-09). AlphaMissense: likely benign (0.0688); Very rare (popmax 0.00666%, amr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Asp668Asn (c.2002G>A)?

SUN2 p.Asp668Asn (c.2002G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Asp668Asn (c.2002G>A) in the general population?

SUN2 p.Asp668Asn (c.2002G>A) is very rare (popmax 0.00666%, amr) (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.Asp668Asn (c.2002G>A)?

AlphaMissense predicts likely benign (score 0.0688) — an in-silico prediction, not a clinical call.

SUN2 p.Asp668Asn

c.2002G>A · rs549404842 · VCV1447692

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 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	0.0688	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP 0.059, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 1,960 bp · p 0.7 · regional, not allelic
Overall
CADD	17.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% Admixed American · 4/60,016 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00372% 60/1,613,956 alleles · very rare exomes 52/1,461,706 · genomes 8/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,004
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.00415%	24,082
East Asian	0.00223%	44,880
South Asian	0.0022%	45,544
African / African-American	0.00133%	75,002

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.Asp668Asn
Coding: c.2002G>A
MANE Select: NM_015374
dbSNP: rs549404842
Type: single nucleotide variant
Location: chr22:38738211 (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-asp668asn (accessed [today's date]).

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