Is NEB p.Arg7443Pro (c.22328G>C) pathogenic?

NEB p.Arg7443Pro (c.22328G>C) is classified Uncertain significance in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-05). AlphaMissense: likely pathogenic (0.9912); Absent from gnomAD v4.1; Associated with nemaline myopathy 2.

What condition is associated with NEB p.Arg7443Pro (c.22328G>C)?

NEB p.Arg7443Pro (c.22328G>C) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Arg7443Pro (c.22328G>C) in the general population?

NEB p.Arg7443Pro (c.22328G>C) is absent from gnomAD v4.1 (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

What do computational predictors say about NEB p.Arg7443Pro (c.22328G>C)?

AlphaMissense predicts likely pathogenic (score 0.9912) — an in-silico prediction, not a clinical call.

NEB p.Arg7443Pro

c.22328G>C · rs2084210932 · VCV957047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9912 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

nemaline myopathy 2

Computational evidence

Protein change
AlphaMissense	0.9912	likely pathogenic · top 1% in NEB
REVEL	0.491	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R5742P vs ClinVar R7443P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NEB
Protein: p.Arg7443Pro
Coding: c.22328G>C
MANE Select: NM_001164508
dbSNP: rs2084210932
Type: single nucleotide variant
Location: chr2:151524561 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 7443: 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.Arg7443Ter Pathogenic/Likely pathogenic ★★ same residue
NEB p.Arg7443Gln Uncertain significance ★★ same residue
NEB p.Arg7443= Likely benign ★ 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-arg7443pro (accessed [today's date]).

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