Is NEB p.Ser7883= (c.23649G>A) pathogenic?

NEB p.Ser7883= (c.23649G>A) is classified Uncertain significance in NEB (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-19). Very rare (popmax 0.00669%, eas); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Ser7883= (c.23649G>A)?

NEB p.Ser7883= (c.23649G>A) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Ser7883= (c.23649G>A) in the general population?

NEB p.Ser7883= (c.23649G>A) is very rare (popmax 0.00669%, 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.Ser7883=

c.23649G>A · rs778102984 · VCV1472326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.392	indeterminate
Splicing
SpliceAI	Δ0.91	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.77	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 0.4, phastCons 1
Overall
CADD	18.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,852 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000809% 13/1,606,962 alleles · very rare exomes 12/1,454,794 · genomes 1/152,168 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,951
European (non-Finnish)	0.000852%	117,363

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.Ser7883=
Coding: c.23649G>A
MANE Select: NM_001164508
dbSNP: rs778102984
Type: single nucleotide variant
Location: chr2:151506166 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 7883: 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.Ser7883Leu Conflicting classifications of pathogenicity ★ same residue
NEB p.Ser7883Pro Uncertain significance ★ same residue
NEB p.Ser7883Trp Uncertain significance ★ 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

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-ser7883 (accessed [today's date]).

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