Is NEB p.Pro8086= (c.24258C>T) pathogenic?

NEB p.Pro8086= (c.24258C>T) is classified Likely benign in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Very rare (popmax 0.00907%, eas); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Pro8086= (c.24258C>T)?

NEB p.Pro8086= (c.24258C>T) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Pro8086= (c.24258C>T) in the general population?

NEB p.Pro8086= (c.24258C>T) is very rare (popmax 0.00907%, eas) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Pro8086=

c.24258C>T · rs1400587382 · VCV1130124

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00907%, eas)

Conditions

nemaline myopathy 2

⚠ 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.
REVEL	0.186	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00907% East Asian · 4/44,116 alleles

Filtering AF 0.00301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00182%

Overall 0.0024% 38/1,584,000 alleles · very rare exomes 36/1,432,356 · genomes 2/151,644 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00907%	11,029
European (non-Finnish)	0.00275%	36,345
African / African-American	0.00134%	74,376
South Asian	0.00115%	86,830

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: NEB
Protein: p.Pro8086=
Coding: c.24258C>T
MANE Select: NM_001164508
dbSNP: rs1400587382
Type: single nucleotide variant
Location: chr2:151497668 (GRCh38)

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

Disease context

nemaline myopathy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe congenital nemaline myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 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/neb-p-pro8086 (accessed [today's date]).

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