Is NEB p.Ser290fs (c.870_873del) pathogenic?

NEB p.Ser290fs (c.870873del) is classified Pathogenic in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Absent from gnomAD; Associated with nemaline myopathy 2.

What condition is associated with NEB p.Ser290fs (c.870_873del)?

NEB p.Ser290fs (c.870_873del) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Ser290fs (c.870_873del) in the general population?

NEB p.Ser290fs (c.870_873del) is absent from gnomAD (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Ser290fs

c.870_873del · rs2150050727 · VCV1685967

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 182
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NEB
Protein: p.Ser290fs
Coding: c.870_873del
MANE Select: NM_001164508
dbSNP: rs2150050727
Type: Deletion
Location: chr2:151710488 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)

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)

Similar variants

NEB p.Ser290= Likely benign ★ same residue
NEB p.Ala339fs Uncertain significance ★★★ same condition
NEB c.1570-2del Pathogenic/Likely pathogenic ★★ same condition
NEB c.22272+2_22272+3del Likely pathogenic ★★ same condition
NEB c.3252_3255+3del Pathogenic/Likely pathogenic ★★ same condition
NEB c.403-6_405del Likely pathogenic ★★ same condition
NEB c.5032-1del Likely pathogenic ★★ same condition
NEB p.Ala1542fs Pathogenic/Likely pathogenic ★★ 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/neb-p-ser290fs (accessed [today's date]).

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