Is NBAS p.Phe167fs (c.500_501del) pathogenic?

NBAS p.Phe167fs (c.500501del) is classified Pathogenic in NBAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-08). Very rare (popmax 0.000847%, nfe); Associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.

What condition is associated with NBAS p.Phe167fs (c.500_501del)?

NBAS p.Phe167fs (c.500_501del) is associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (ClinVar).

How common is NBAS p.Phe167fs (c.500_501del) in the general population?

NBAS p.Phe167fs (c.500_501del) is very rare (popmax 0.000847%, nfe) (gnomAD).

NBAS p.Phe167fs

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.500_501del · rs1232631800 · VCV2159340

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

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 7 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.85, phastCons 1
Overall
CADD	33.0	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 0.000847% European (non-Finnish) · 10/1,180,030 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,614,040 alleles · very rare exomes 10/1,461,860 · genomes 1/152,180 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,024
European (non-Finnish)grpmax	0.000847%	118,003

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe167fs
Coding: c.500_501del
MANE Select: NM_015909
dbSNP: rs1232631800
Type: Deletion
Location: chr2:15539235 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 167: the 'interaction with use1' 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

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NBAS p.Ser1567fs Likely 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-phe167fs (accessed [today's date]).

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