Is NBAS p.Ser1419fs (c.4255del) pathogenic?

NBAS p.Ser1419fs (c.4255del) is classified Pathogenic in NBAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-11). Very rare (popmax 0.00659%, sas); Associated with infantile liver failure syndrome 2.

What condition is associated with NBAS p.Ser1419fs (c.4255del)?

NBAS p.Ser1419fs (c.4255del) is associated with infantile liver failure syndrome 2, optic nerve disorder, short stature-optic atrophy-Pelger-Huët anomaly syndrome (ClinVar).

How common is NBAS p.Ser1419fs (c.4255del) in the general population?

NBAS p.Ser1419fs (c.4255del) is very rare (popmax 0.00659%, sas) (gnomAD).

NBAS p.Ser1419fs

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.4255del · rs768154511 · VCV2441821

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

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 36 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,084 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00041% 6/1,461,778 alleles · very rare

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.Ser1419fs
Coding: c.4255del
MANE Select: NM_015909
dbSNP: rs768154511
Type: Deletion
Location: chr2:15330690 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1419: 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); 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 collagen secretion; diffuse collagen bundles; reduced protein expression in fibroblasts); the 'interaction with zw10 and rint1' 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

Also linked: optic nerve disorder short stature-optic atrophy-Pelger-Huët anomaly syndrome

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 c.4657_4659+18del Likely pathogenic ★ same condition
NBAS c.(?_5028 Likely pathogenic ★ same condition
NBAS p.Ala1686fs Likely pathogenic ★ same condition
NBAS p.Lys1169fs Likely pathogenic ★ same condition
NBAS p.Phe1701_Met1702insTer 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-ser1419fs (accessed [today's date]).

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