Is NEB p.Pro7370= (c.22110A>G) pathogenic?

NEB p.Pro7370= (c.22110A>G) is classified Conflicting classifications of pathogenicity in NEB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-07). Ultra-rare (popmax 0.0891%, eas); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Pro7370= (c.22110A>G)?

NEB p.Pro7370= (c.22110A>G) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Pro7370= (c.22110A>G) in the general population?

NEB p.Pro7370= (c.22110A>G) is ultra-rare (popmax 0.0891%, 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.Pro7370=

c.22110A>G · rs539800267 · VCV194144

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0891%, eas)

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 -13	GERP -5.5
Overall
CADD	0.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0891% East Asian · 40/44,890 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00273% 44/1,614,010 alleles · ultra-rare exomes 38/1,461,680 · genomes 6/152,330 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0891%	1,122
Admixed American	0.00333%	30,010
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Pro7370=
Coding: c.22110A>G
MANE Select: NM_001164508
dbSNP: rs539800267
Type: single nucleotide variant
Location: chr2:151526009 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 7370: 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.Pro7370Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
NEB p.Pro7370Arg 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-pro7370 (accessed [today's date]).

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