Is NBAS p.Gln1985Ter (c.5953C>T) pathogenic?

NBAS p.Gln1985Ter (c.5953C>T) is classified Likely pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). Very rare (popmax 0.0011%, sas); Associated with infantile liver failure syndrome 2.

What condition is associated with NBAS p.Gln1985Ter (c.5953C>T)?

NBAS p.Gln1985Ter (c.5953C>T) is associated with infantile liver failure syndrome 2 (ClinVar).

How common is NBAS p.Gln1985Ter (c.5953C>T) in the general population?

NBAS p.Gln1985Ter (c.5953C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

NBAS p.Gln1985Ter

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.5953C>T · VCV3362360

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, 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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 46 of 52
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.4, phastCons 0.97
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Overall 6.84e-05% 1/1,461,748 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.Gln1985Ter
Coding: c.5953C>T
MANE Select: NM_015909
Type: single nucleotide variant
Location: chr2:15234738 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1985: 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

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

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

NBAS c.173-2A>G Likely pathogenic ★★ same condition
NBAS c.2423+404G>C Likely pathogenic ★★ same condition
NBAS c.4583-2A>G Likely pathogenic ★★ same condition
NBAS c.513+2T>C Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Arg1004Ter Pathogenic ★★ same condition
NBAS p.Arg1236Ter Pathogenic/Likely pathogenic ★★ same condition
NBAS p.Arg136Gly Likely pathogenic ★★ same condition
NBAS p.Arg137Trp 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-gln1985ter (accessed [today's date]).

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