Is NBAS p.Ser1567fs (c.4698_4741del) pathogenic?

NBAS p.Ser1567fs (c.46984741del) is classified Likely pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-20). Absent from gnomAD; Associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.

What condition is associated with NBAS p.Ser1567fs (c.4698_4741del)?

NBAS p.Ser1567fs (c.4698_4741del) is associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (ClinVar).

How common is NBAS p.Ser1567fs (c.4698_4741del) in the general population?

NBAS p.Ser1567fs (c.4698_4741del) is absent from gnomAD (gnomAD).

NBAS p.Ser1567fs

Q: How is Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins inherited?

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

c.4698_4741del · rs2528283195 · VCV1722435

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

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 40 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NBAS
Protein: p.Ser1567fs
Coding: c.4698_4741del
MANE Select: NM_015909
dbSNP: rs2528283195
Type: Deletion
Location: chr2:15308272 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1567: 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

acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

NBAS p.Ile984fs Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Leu1507fs Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Phe167fs Pathogenic ★★ same condition
NBAS p.Trp1850fs Pathogenic ★★ same condition
NBAS p.Ile512fs Conflicting classifications of pathogenicity ★ same condition
NBAS p.Leu2293fs Conflicting classifications of pathogenicity ★ same condition
NBAS c.1726-2A>G Likely pathogenic ★★ same condition
NBAS c.4461+2T>C 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-ser1567fs (accessed [today's date]).

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