Is SUN2 p.Arg620His (c.1859G>A) pathogenic?

SUN2 p.Arg620His (c.1859G>A) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely benign (0.0588); Ultra-rare (popmax 0.0267%, eas); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg620His (c.1859G>A)?

SUN2 p.Arg620His (c.1859G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Arg620His (c.1859G>A) in the general population?

SUN2 p.Arg620His (c.1859G>A) is ultra-rare (popmax 0.0267%, 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.Arg620His (c.1859G>A)?

AlphaMissense predicts likely benign (score 0.0588) — an in-silico prediction, not a clinical call.

SUN2 p.Arg620His

c.1859G>A · rs566312173 · VCV1399348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0588 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

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	0.0588	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.68	GERP -3.2, phastCons 0.008
Regional constraint	o/e 0.70	unconstrained · MANE · 2,037 bp · p 3.5e-07 · regional, not allelic
Overall
CADD	21.1	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 0.0267% East Asian · 12/44,894 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00434% 70/1,613,744 alleles · ultra-rare exomes 61/1,461,560 · genomes 9/152,184 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
African / African-American	0.00534%	18,732
European (non-Finnish)	0.00432%	23,138
Remaining individualsnot grpmax-eligible	0.0032%	31,238
South Asian	0.0011%	91,086

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.Arg620His
Coding: c.1859G>A
MANE Select: NM_015374
dbSNP: rs566312173
Type: single nucleotide variant
Location: chr22:38738675 (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-arg620his (accessed [today's date]).

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