Is SYNE2 p.Ser1237= (c.3711G>A) pathogenic?

SYNE2 p.Ser1237= (c.3711G>A) is classified Likely benign in SYNE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-04). Very rare (popmax 0.00223%, eas); Associated with Emery-Dreifuss muscular dystrophy 5, autosomal dominant.

What condition is associated with SYNE2 p.Ser1237= (c.3711G>A)?

SYNE2 p.Ser1237= (c.3711G>A) is associated with Emery-Dreifuss muscular dystrophy 5, autosomal dominant (ClinVar).

How common is SYNE2 p.Ser1237= (c.3711G>A) in the general population?

SYNE2 p.Ser1237= (c.3711G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

SYNE2 p.Ser1237=

c.3711G>A · rs773704983 · VCV955570

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.2
Overall
CADD	0.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,866 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00093% 15/1,613,146 alleles · very rare exomes 14/1,461,144 · genomes 1/152,002 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
European (non-Finnish)	0.00119%	84,272

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: SYNE2
Protein: p.Ser1237=
Coding: c.3711G>A
MANE Select: NM_182914
dbSNP: rs773704983
Type: single nucleotide variant
Location: chr14:64002006 (GRCh38)
Gene constraint: LOEUF 0.516 · pLI <0.01 (gnomAD)

Full SYNE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Emery-Dreifuss muscular dystrophy 5, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SYNE2 p.Ser1237Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SYNE2 c.12108+3A>G Uncertain significance ★★ same condition
SYNE2 c.12609+1G>A Uncertain significance ★★ same condition
SYNE2 c.13159-3C>T Uncertain significance ★★ same condition
SYNE2 c.13159-7A>G Uncertain significance ★★ same condition
SYNE2 c.15484-3T>C Uncertain significance ★★ same condition
SYNE2 c.2313+1G>A Uncertain significance ★★ same condition
SYNE2 c.2647-2A>G 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/syne2-p-ser1237 (accessed [today's date]).

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