Is NBAS p.Arg797Ter (c.2389C>T) pathogenic?

NBAS p.Arg797Ter (c.2389C>T) is classified Pathogenic/Likely pathogenic in NBAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-15). Very rare (popmax 0.000424%, nfe); Associated with short stature-optic atrophy-Pelger-Huët anomaly syndrome.

How common is NBAS p.Arg797Ter (c.2389C>T) in the general population?

NBAS p.Arg797Ter (c.2389C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

NBAS p.Arg797Ter

Q: What condition is associated with NBAS p.Arg797Ter (c.2389C>T)?

NBAS p.Arg797Ter (c.2389C>T) is associated with short stature-optic atrophy-Pelger-Huët anomaly syndrome, infantile liver failure syndrome 2 (ClinVar).

c.2389C>T · rs1268309894 · VCV1373796

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

short stature-optic atrophy-Pelger-Huët anomaly syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 22 of 52
Splicing
SpliceAI	Δ0.49	acceptor loss, 49 bp away · masked 0 · deltas
Pangolin	Δ0.57	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.4	GERP 0.43, phastCons 1
Overall
CADD	38.0	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 0.000424% European (non-Finnish) · 5/1,179,692 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,302 alleles · very rare exomes 6/1,461,236 · genomes 0/152,066 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)grpmax	0.000424%	235,939

Remaining individuals 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.Arg797Ter
Coding: c.2389C>T
MANE Select: NM_015909
dbSNP: rs1268309894
Type: single nucleotide variant
Location: chr2:15427745 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 797: 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

short stature-optic atrophy-Pelger-Huët anomaly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: infantile liver failure syndrome 2

Similar variants

NBAS p.Arg797Gln Uncertain significance ★★ ⚠ same residue
NBAS c.173-2A>G Likely pathogenic ★★ same condition
NBAS c.2423+404G>C Likely pathogenic ★★ same condition
NBAS c.335+1G>C Pathogenic/Likely pathogenic ★★ same condition
NBAS c.4583-2A>G Likely pathogenic ★★ same condition
NBAS c.513+2T>C Pathogenic/Likely pathogenic ★★ same condition
NBAS c.886-5T>A Likely pathogenic ★★ same condition
NBAS p.Arg1004Ter 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-arg797ter (accessed [today's date]).

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