Is SYNE2 p.Pro5= (c.15T>C) pathogenic?

SYNE2 p.Pro5= (c.15T>C) is classified Likely benign in SYNE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-11). Very rare (popmax 0.00017%, nfe); Associated with Emery-Dreifuss muscular dystrophy 5, autosomal dominant.

What condition is associated with SYNE2 p.Pro5= (c.15T>C)?

SYNE2 p.Pro5= (c.15T>C) is associated with Emery-Dreifuss muscular dystrophy 5, autosomal dominant (ClinVar).

How common is SYNE2 p.Pro5= (c.15T>C) in the general population?

SYNE2 p.Pro5= (c.15T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

SYNE2 p.Pro5=

c.15T>C · rs2153351102 · VCV1151436

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 -1.7
Overall
CADD	2.938	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,882 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,610,456 alleles · very rare exomes 2/1,458,412 · genomes 0/152,044 · joint denominator

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.Pro5=
Coding: c.15T>C
MANE Select: NM_182914
dbSNP: rs2153351102
Type: single nucleotide variant
Location: chr14:63909163 (GRCh38)
Gene constraint: LOEUF 0.516 · pLI <0.01 (gnomAD)
Residue 5: the 'actin-binding' region

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 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
SYNE2 c.5960+6G>A 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-pro5 (accessed [today's date]).

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