Is NEB p.Val8430= (c.25290C>T) pathogenic?

NEB p.Val8430= (c.25290C>T) is classified Likely benign in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-23). Absent from gnomAD v4.1; Associated with nemaline myopathy 2.

What condition is associated with NEB p.Val8430= (c.25290C>T)?

NEB p.Val8430= (c.25290C>T) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Val8430= (c.25290C>T) in the general population?

NEB p.Val8430= (c.25290C>T) is absent from gnomAD v4.1 (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Val8430=

c.25290C>T · rs2551667362 · VCV2992743

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,124)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.092	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -3.5, phastCons 0.014
Overall
CADD	0.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,589,124). 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.Val8430=
Coding: c.25290C>T
MANE Select: NM_001164508
dbSNP: rs2551667362
Type: single nucleotide variant
Location: chr2:151490379 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 8430: the 'interaction with svil' region; a UniProt-annotated variant site (in amc6)

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.Val8430Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
NEB c.11910+1G>A Likely pathogenic ★★★ same condition
NEB c.6076-1G>T Likely pathogenic ★★★ same condition
NEB c.78+1G>A Pathogenic ★★★ same condition
NEB p.Arg2313Ter Pathogenic ★★★ same condition
NEB p.Asp498Gly Likely pathogenic ★★★ ⚠ same condition
NEB p.Ser6366Ile Pathogenic ★★★ same condition
NEB p.Ser6648= 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-val8430 (accessed [today's date]).

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