Is NEB p.Ser8007= (c.24021G>A) pathogenic?

NEB p.Ser8007= (c.24021G>A) is classified Conflicting classifications of pathogenicity in NEB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-30). Very rare (popmax 0.0059%, amr); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Ser8007= (c.24021G>A)?

NEB p.Ser8007= (c.24021G>A) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Ser8007= (c.24021G>A) in the general population?

NEB p.Ser8007= (c.24021G>A) is very rare (popmax 0.0059%, amr) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Ser8007=

c.24021G>A · rs557688789 · VCV1352686

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0059%, amr)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.073	moderately benign-leaning
Splicing
SpliceAI	Δ0.31	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0059% Admixed American · 3/50,856 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000834%

Overall 0.000584% 9/1,541,718 alleles · very rare exomes 6/1,389,780 · genomes 3/151,938 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0059%	16,952
African / African-American	0.00275%	36,376
South Asian	0.0024%	41,624
European (non-Finnish)	0.000176%	569,557

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.Ser8007=
Coding: c.24021G>A
MANE Select: NM_001164508
dbSNP: rs557688789
Type: single nucleotide variant
Location: chr2:151501391 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 8007: 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.Ser8007Ter Pathogenic ★ same residue
NEB p.Ser8007Leu 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

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-ser8007 (accessed [today's date]).

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