Is SUN2 p.Gly671Ser (c.2011G>A) pathogenic?

SUN2 p.Gly671Ser (c.2011G>A) is classified Benign in SUN2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1914); Common (popmax 16%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Emery-Dreifuss muscular dystrophy.

What condition is associated with SUN2 p.Gly671Ser (c.2011G>A)?

SUN2 p.Gly671Ser (c.2011G>A) 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.Gly671Ser (c.2011G>A)?

AlphaMissense predicts likely benign (score 0.1914) — an in-silico prediction, not a clinical call.

SUN2 p.Gly671Ser

Q: How common is SUN2 p.Gly671Ser (c.2011G>A) in the general population?

SUN2 p.Gly671Ser (c.2011G>A) is common (popmax 16%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2011G>A · rs2072797 · VCV1168063

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1914 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 16%, 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	0.1914	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -10.08	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 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,960 bp · p 0.7 · regional, not allelic
Overall
CADD	25.8	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 16% East Asian · 7,187/44,862 alleles

Filtering AF 15.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.6%

Overall 11% 177,898/1,613,644 alleles · common exomes 164,218/1,461,496 · genomes 13,680/152,148 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	23.3%	4
East Asiangrpmax	16%	6
Finnishnot grpmax-eligible	16%	6
South Asian	12.1%	8
European (non-Finnish)	11.4%	9
Remaining individualsnot grpmax-eligible	10.6%	9
Middle Eastern	10.4%	10
Ashkenazi Jewishnot grpmax-eligible	9.25%	11
Admixed American	5.42%	18
African / African-American	1.91%	52

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly671Ser
Coding: c.2011G>A
MANE Select: NM_015374
dbSNP: rs2072797
Type: single nucleotide variant
Location: chr22:38738202 (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-gly671ser (accessed [today's date]).

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