Is NBEA p.Pro2582= (c.7746G>T) pathogenic?

NBEA p.Pro2582= (c.7746G>T) is classified Likely benign in NBEA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Very rare (popmax 0.0011%, sas); Associated with NBEA-related disorder.

What condition is associated with NBEA p.Pro2582= (c.7746G>T)?

NBEA p.Pro2582= (c.7746G>T) is associated with NBEA-related disorder (ClinVar).

How common is NBEA p.Pro2582= (c.7746G>T) in the general population?

NBEA p.Pro2582= (c.7746G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

NBEA p.Pro2582=

c.7746G>T · rs146396146 · VCV3049701

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

NBEA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -2.3
Overall
CADD	0.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,958 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000868% 14/1,613,600 alleles · very rare exomes 14/1,461,336 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,235
South Asiangrpmax	0.0011%	90,958
European (non-Finnish)	0.000932%	107,246

Remaining individuals 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: NBEA
Protein: p.Pro2582=
Coding: c.7746G>T
MANE Select: NM_001385012
dbSNP: rs146396146
Type: single nucleotide variant
Location: chr13:35646324 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2582: a UniProt-annotated variant site (in nedege); a UniProt-annotated variant site (in nedege; uncertain significance)

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

Disease context

NBEA-related disorder

Similar variants

NBEA p.Pro2582Leu Uncertain significance ★ same residue
NBEA p.Pro2582Ser Uncertain significance ★ ⚠ same residue
NBEA p.Arg145Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Arg696Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Asp319Tyr Likely pathogenic ★★ same condition
NBEA p.Glu1995Lys Uncertain significance ★★ same condition
NBEA p.Gly41Ala Uncertain significance ★★ ⚠ same condition
NBEA c.2651+1G>A 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/nbea-p-pro2582 (accessed [today's date]).

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