Is SUN2 p.Arg156Gln (c.467G>A) pathogenic?

SUN2 p.Arg156Gln (c.467G>A) is classified Likely benign in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). AlphaMissense: likely benign (0.0919); Rare (popmax 0.368%, afr); Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Arg156Gln (c.467G>A)?

SUN2 p.Arg156Gln (c.467G>A) is associated with Emery-Dreifuss muscular dystrophy (ClinVar).

How common is SUN2 p.Arg156Gln (c.467G>A) in the general population?

SUN2 p.Arg156Gln (c.467G>A) is rare (popmax 0.368%, 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.Arg156Gln (c.467G>A)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

SUN2 p.Arg156Gln

c.467G>A · rs137925849 · VCV530845

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.368%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP 0.15
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	17.56	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 0.368% African / African-American · 276/75,054 alleles

Filtering AF 0.332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.318%

Overall 0.022% 355/1,613,840 alleles · rare exomes 179/1,461,506 · genomes 176/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.368%	272
Admixed American	0.05%	2,001
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Middle Eastern	0.0165%	6,062
Finnishnot grpmax-eligible	0.00784%	12,754
East Asian	0.00446%	22,437
South Asian	0.00439%	22,772
European (non-Finnish)	0.00169%	58,997

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.Arg156Gln
Coding: c.467G>A
MANE Select: NM_015374
dbSNP: rs137925849
Type: single nucleotide variant
Location: chr22:38750278 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB

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)

Similar variants

SUN2 p.Ala158Thr Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala251Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala508Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Ala56Val Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg100Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Gln Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg102Trp Uncertain significance ★★ ⚠ same condition
SUN2 p.Arg104Lys Uncertain significance ★★ ⚠ same condition

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-arg156gln (accessed [today's date]).

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