Is NEB p.Ser7173= (c.21519C>T) pathogenic?

NEB p.Ser7173= (c.21519C>T) is classified Benign in NEB (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.93%, afr); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Ser7173= (c.21519C>T)?

NEB p.Ser7173= (c.21519C>T) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Ser7173= (c.21519C>T) in the general population?

NEB p.Ser7173= (c.21519C>T) is low-frequency (popmax 2.93%, afr) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Ser7173=

c.21519C>T · rs16830170 · VCV129725

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.93%, afr)

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.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.1	GERP -5.3
Overall
CADD	4.859	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.93% African / African-American · 2,193/74,848 alleles

Filtering AF 2.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.79%

Overall 0.383% 6,157/1,606,344 alleles · low-frequency exomes 4,653/1,454,064 · genomes 1,504/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.93%	34
South Asian	2.69%	37
East Asian	1.34%	74
Remaining individualsnot grpmax-eligible	0.454%	220
Middle Eastern	0.248%	403
Admixed American	0.216%	464
European (non-Finnish)	0.0417%	2,396
Finnishnot grpmax-eligible	0.0344%	2,904

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.Ser7173=
Coding: c.21519C>T
MANE Select: NM_001164508
dbSNP: rs16830170
Type: single nucleotide variant
Location: chr2:151531795 (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-ser7173 (accessed [today's date]).

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