Is NBEAL2 p.Pro2018= (c.6054C>G) pathogenic?

NBEAL2 p.Pro2018= (c.6054C>G) is classified Benign/Likely benign in NBEAL2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-01). Common (popmax 57.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with gray platelet syndrome.

What condition is associated with NBEAL2 p.Pro2018= (c.6054C>G)?

NBEAL2 p.Pro2018= (c.6054C>G) is associated with gray platelet syndrome (ClinVar).

How is Gray platelet syndrome inherited?

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

NBEAL2 p.Pro2018=

Q: How common is NBEAL2 p.Pro2018= (c.6054C>G) in the general population?

NBEAL2 p.Pro2018= (c.6054C>G) is common (popmax 57.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6054C>G · rs1079276 · VCV260586

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 57.8%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

gray platelet syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.046	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP 0.68, phastCons 0.16
Overall
CADD	3.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 57.8% European (non-Finnish) · 682,320/1,179,720 alleles

Filtering AF 57.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.7%

Overall 55.7% 899,164/1,613,396 alleles · common exomes 825,292/1,461,458 · genomes 73,872/151,938 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	60.8%	2
European (non-Finnish)grpmax	57.8%	2
East Asian	56.4%	2
Remaining individualsnot grpmax-eligible	54.5%	2
South Asian	54.1%	2
Ashkenazi Jewishnot grpmax-eligible	51.9%	2
Admixed American	49.8%	2
Middle Eastern	45.9%	2
Amishnot grpmax-eligible	42.1%	2
African / African-American	28.1%	4

Finnish 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.Pro2018=
Coding: c.6054C>G
MANE Select: NM_015175
dbSNP: rs1079276
Type: single nucleotide variant
Location: chr3:47004249 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI <0.01 (gnomAD)
Residue 2018: the beach-type ph domain

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 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
NBEAL2 c.*267G>C 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-pro2018 (accessed [today's date]).

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