Is NEB p.Arg880= (c.2640C>T) pathogenic?

NEB p.Arg880= (c.2640C>T) is classified Benign/Likely benign in NEB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-24). Low-frequency (popmax 1.37%, afr); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Arg880= (c.2640C>T)?

NEB p.Arg880= (c.2640C>T) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Arg880= (c.2640C>T) in the general population?

NEB p.Arg880= (c.2640C>T) is low-frequency (popmax 1.37%, 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.Arg880=

c.2640C>T · rs114959904 · VCV129737

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, afr)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -4.3
Overall
CADD	4.894	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.37% African / African-American · 1,027/74,814 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0793% 1,266/1,596,906 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.37%	73
Middle Eastern	0.0993%	1,007
Remaining individualsnot grpmax-eligible	0.0968%	1,033
Admixed American	0.0589%	1,698
East Asian	0.0224%	4,456
European (non-Finnish)	0.0106%	9,435
South Asian	0.00566%	17,668

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.Arg880=
Coding: c.2640C>T
MANE Select: NM_001164508
dbSNP: rs114959904
Type: single nucleotide variant
Location: chr2:151684973 (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.Arg880Cys Uncertain significance ★★ ⚠ same residue
NEB p.Arg880His Uncertain significance ★★ ⚠ same residue
NEB p.Arg880_Glu881delinsGln 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-arg880 (accessed [today's date]).

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