Is NEB p.Arg6063Gln (c.18188G>A) pathogenic?

NEB p.Arg6063Gln (c.18188G>A) is classified Uncertain significance in NEB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-07). AlphaMissense: likely benign (0.2266); Very rare (popmax 0.00447%, eas); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Arg6063Gln (c.18188G>A)?

NEB p.Arg6063Gln (c.18188G>A) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Arg6063Gln (c.18188G>A) in the general population?

NEB p.Arg6063Gln (c.18188G>A) is very rare (popmax 0.00447%, eas) (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.Arg6063Gln (c.18188G>A)?

AlphaMissense predicts likely benign (score 0.2266) — an in-silico prediction, not a clinical call.

NEB p.Arg6063Gln

c.18188G>A · rs752344851 · VCV2141595

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
AlphaMissense	0.2266	likely benign
REVEL	0.435	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	24.9	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 R4362Q vs ClinVar R6063Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,756 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000869% 14/1,611,602 alleles · very rare exomes 14/1,459,352 · genomes 0/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,378
African / African-American	0.00133%	74,974
European (non-Finnish)	0.000933%	107,171

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.Arg6063Gln
Coding: c.18188G>A
MANE Select: NM_001164508
dbSNP: rs752344851
Type: single nucleotide variant
Location: chr2:151565789 (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.Arg6063Ter Pathogenic ★★ 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
NEB p.Ser6648= 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-arg6063gln (accessed [today's date]).

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