Is NBEAL2 p.Arg792Gln (c.2375G>A) pathogenic?

NBEAL2 p.Arg792Gln (c.2375G>A) is classified Conflicting classifications of pathogenicity in NBEAL2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-09). AlphaMissense: likely benign (0.0754); Rare (popmax 0.135%, mid); Associated with Inborn genetic diseases.

What condition is associated with NBEAL2 p.Arg792Gln (c.2375G>A)?

NBEAL2 p.Arg792Gln (c.2375G>A) is associated with Inborn genetic diseases, thrombocytopenia, gray platelet syndrome (ClinVar).

How common is NBEAL2 p.Arg792Gln (c.2375G>A) in the general population?

NBEAL2 p.Arg792Gln (c.2375G>A) is rare (popmax 0.135%, mid) (gnomAD).

What do computational predictors say about NBEAL2 p.Arg792Gln (c.2375G>A)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

NBEAL2 p.Arg792Gln

c.2375G>A · rs140354422 · VCV345637

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -5.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 24 kb · p 4.7e-09 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% Middle Eastern · 8/5,940 alleles

Filtering AF 0.0914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0895%

Overall 0.0852% 1,351/1,585,618 alleles · rare exomes 1,253/1,433,338 · genomes 98/152,280 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.374%	267
Middle Easterngrpmax	0.135%	743
European (non-Finnish)	0.0961%	1,041
Remaining individualsnot grpmax-eligible	0.0801%	1,249
South Asian	0.0397%	2,519
Admixed American	0.026%	3,839
African / African-American	0.0174%	5,738
Finnishnot grpmax-eligible	0.00978%	10,223
East Asian	0.00227%	44,080

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.Arg792Gln
Coding: c.2375G>A
MANE Select: NM_015175
dbSNP: rs140354422
Type: single nucleotide variant
Location: chr3:46996494 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombocytopenia gray platelet syndrome

Similar variants

NBEAL2 p.Arg792= Benign/Likely benign ★★ 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-arg792gln (accessed [today's date]).

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