Is NBAS p.Ser976fs (c.2926del) pathogenic?

NBAS p.Ser976fs (c.2926del) is classified Likely pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-28). Associated with infantile liver failure syndrome 2.

What condition is associated with NBAS p.Ser976fs (c.2926del)?

NBAS p.Ser976fs (c.2926del) is associated with infantile liver failure syndrome 2 (ClinVar).

NBAS p.Ser976fs

Q: How is Fever-associated acute infantile liver failure syndrome inherited?

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

c.2926del · VCV4072085

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

infantile liver failure syndrome 2

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 25 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

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

Variant & gene context

Gene: NBAS
Protein: p.Ser976fs
Coding: c.2926del
MANE Select: NM_015909
Type: Deletion
Location: chr2:15415557 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 976: 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

infantile liver failure syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fever-associated acute infantile liver failure syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

NBAS p.Asp2149_Ile2150insTer Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Ile984fs Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Leu1726fs Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Ser1419fs Pathogenic ★★ same condition
NBAS c.4657_4659+18del Likely pathogenic ★ same condition
NBAS p.Ala1686fs Likely pathogenic ★ same condition
NBAS p.Lys1169fs Likely pathogenic ★ same condition
NBAS p.Phe1754fs 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-ser976fs (accessed [today's date]).

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