Is NBEAL2 p.Arg792= (c.2376G>A) pathogenic?

NBEAL2 p.Arg792= (c.2376G>A) is classified Benign/Likely benign in NBEAL2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-30). Rare (popmax 0.46%, nfe); Associated with gray platelet syndrome.

What condition is associated with NBEAL2 p.Arg792= (c.2376G>A)?

NBEAL2 p.Arg792= (c.2376G>A) is associated with gray platelet syndrome (ClinVar).

How common is NBEAL2 p.Arg792= (c.2376G>A) in the general population?

NBEAL2 p.Arg792= (c.2376G>A) is rare (popmax 0.46%, nfe) (gnomAD).

How is Gray platelet syndrome inherited?

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

NBEAL2 p.Arg792=

c.2376G>A · rs200489667 · VCV345638

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.46%, nfe)

Conditions

gray platelet syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.91	GERP -3.5
Overall
CADD	7.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.46% European (non-Finnish) · 5,355/1,163,562 alleles

Filtering AF 0.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.446%

Overall 0.384% 6,084/1,585,830 alleles · rare exomes 5,705/1,433,506 · genomes 379/152,324 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.582%	172
Remaining individualsnot grpmax-eligible	0.465%	215
European (non-Finnish)grpmax	0.46%	217
Admixed American	0.222%	450
Finnishnot grpmax-eligible	0.14%	713
African / African-American	0.0764%	1,309
Middle Eastern	0.0336%	2,976
South Asian	0.00567%	17,638
East Asian	0.00227%	44,142

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NBEAL2
Protein: p.Arg792=
Coding: c.2376G>A
MANE Select: NM_015175
dbSNP: rs200489667
Type: single nucleotide variant
Location: chr3:46996495 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI <0.01 (gnomAD)

Full NBEAL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

gray platelet syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gray platelet syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

NBEAL2 p.Arg792Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
NBEAL2 c.4485-1G>A Pathogenic/Likely pathogenic ★★ same condition
NBEAL2 c.4485-1G>T Pathogenic/Likely pathogenic ★★ same condition
NBEAL2 p.Arg2120Gln Likely pathogenic ★★ same condition
NBEAL2 p.Arg597Ter Pathogenic ★★ same condition
NBEAL2 p.Glu1361Ter Pathogenic ★★ same condition
NBEAL2 c.2557-5C>G Uncertain significance ★★ same condition
NBEAL2 c.5459+8G>A Uncertain significance ★★ 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/nbeal2-p-arg792 (accessed [today's date]).

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