Is NBAS p.Pro827fs (c.2479_2498del) pathogenic?

NBAS p.Pro827fs (c.24792498del) is classified Likely pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-14). Very rare (popmax 0.000169%, nfe); Associated with NBAS-related disorder.

What condition is associated with NBAS p.Pro827fs (c.2479_2498del)?

NBAS p.Pro827fs (c.2479_2498del) is associated with NBAS-related disorder (ClinVar).

How common is NBAS p.Pro827fs (c.2479_2498del) in the general population?

NBAS p.Pro827fs (c.2479_2498del) is very rare (popmax 0.000169%, nfe) (gnomAD).

NBAS p.Pro827fs

c.2479_2498del · VCV4953814

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

NBAS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 23 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 1.7, phastCons 0.014

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,006 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,156 alleles · very rare exomes 2/1,461,836 · genomes 0/152,320 · joint denominator

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: NBAS
Protein: p.Pro827fs
Coding: c.2479_2498del
MANE Select: NM_015909
Type: Deletion
Location: chr2:15424394 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 827: a UniProt-annotated variant site (in ilfs2; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance; reduced protein expression levels in fibroblasts); the 'interaction with use1' region

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

Disease context

NBAS-related disorder

Similar variants

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NBAS p.Lys2298fs Likely pathogenic ★ same condition
NBAS p.Thr1254fs Likely pathogenic ★ same condition
NBAS c.4090-10_4090-8del Conflicting classifications of pathogenicity ★ same condition
NBAS c.513+2T>C Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Arg581Ter Pathogenic/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/nbas-p-pro827fs (accessed [today's date]).

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