Is NBEA p.Phe2189fs (c.6564dup) pathogenic?

NBEA p.Phe2189fs (c.6564dup) is classified Pathogenic in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). Associated with neurodevelopmental disorder with or without early-onset generalized epilepsy.

What condition is associated with NBEA p.Phe2189fs (c.6564dup)?

NBEA p.Phe2189fs (c.6564dup) is associated with neurodevelopmental disorder with or without early-onset generalized epilepsy (ClinVar).

NBEA p.Phe2189fs

c.6564dup · VCV4071975

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder with or without early-onset generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 41 of 59
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: NBEA
Protein: p.Phe2189fs
Coding: c.6564dup
MANE Select: NM_001385012
Type: Duplication
Location: chr13:35472513 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2189: the beach-type ph domain; a UniProt-annotated variant site (in nedege); an α-helix

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

Disease context

neurodevelopmental disorder with or without early-onset generalized epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NBEA p.Asn1121fs Likely pathogenic ★★ same condition
NBEA c.4662+2dup Likely pathogenic ★ same condition
NBEA p.Asp1304fs Pathogenic ★ same condition
NBEA p.Thr1610fs Uncertain significance ★ same condition
NBEA p.Lys2040fs Uncertain significance same condition
NBEA p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Arg1493fs Pathogenic ★★ same condition
NBEA p.Arg2866Ter 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-phe2189fs (accessed [today's date]).

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