Is SPEG p.Pro3130= (c.9390G>T) pathogenic?

SPEG p.Pro3130= (c.9390G>T) is classified Benign in SPEG (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 43.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with myopathy, centronuclear, 5.

What condition is associated with SPEG p.Pro3130= (c.9390G>T)?

SPEG p.Pro3130= (c.9390G>T) is associated with myopathy, centronuclear, 5 (ClinVar).

How is Autosomal recessive centronuclear myopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SPEG p.Pro3130=

Q: How common is SPEG p.Pro3130= (c.9390G>T) in the general population?

SPEG p.Pro3130= (c.9390G>T) is common (popmax 43.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9390G>T · rs12473286 · VCV1221215

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 43.8%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

myopathy, centronuclear, 5

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.19	GERP 0.24, phastCons 0.99
Overall
CADD	9.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.8% South Asian · 39,813/90,938 alleles

Filtering AF 43.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.3%

Overall 26.4% 424,679/1,611,190 alleles · common exomes 385,311/1,459,168 · genomes 39,368/152,022 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	43.8%	2
Middle Eastern	34.5%	3
Ashkenazi Jewishnot grpmax-eligible	31.4%	3
Remaining individualsnot grpmax-eligible	27.2%	4
Amishnot grpmax-eligible	26.3%	4
European (non-Finnish)	25.5%	4
African / African-American	24.9%	4
Admixed American	23.8%	4
Finnishnot grpmax-eligible	23.4%	4
East Asian	18.2%	6

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: SPEG
Protein: p.Pro3130=
Coding: c.9390G>T
MANE Select: NM_005876
dbSNP: rs12473286
Type: single nucleotide variant
Location: chr2:219491798 (GRCh38)

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

Disease context

myopathy, centronuclear, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive centronuclear myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

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/speg-p-pro3130 (accessed [today's date]).

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