Is NBAS p.Arg1995Ter (c.5983C>T) pathogenic?

NBAS p.Arg1995Ter (c.5983C>T) is classified Pathogenic/Likely pathogenic in NBAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-16). Very rare (popmax 0.00167%, amr); Associated with short stature-optic atrophy-Pelger-Huët anomaly syndrome.

How common is NBAS p.Arg1995Ter (c.5983C>T) in the general population?

NBAS p.Arg1995Ter (c.5983C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

NBAS p.Arg1995Ter

Q: What condition is associated with NBAS p.Arg1995Ter (c.5983C>T)?

NBAS p.Arg1995Ter (c.5983C>T) is associated with short stature-optic atrophy-Pelger-Huët anomaly syndrome, infantile liver failure syndrome 2 (ClinVar).

c.5983C>T · rs767134813 · VCV2163359

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

short stature-optic atrophy-Pelger-Huët anomaly syndrome

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 6.4	GERP 1.5, phastCons 1
Overall
CADD	45.0	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 0.00167% Admixed American · 1/59,998 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000805% 13/1,613,950 alleles · very rare exomes 12/1,461,834 · genomes 1/152,116 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
European (non-Finnish)	0.00102%	98,331

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.Arg1995Ter
Coding: c.5983C>T
MANE Select: NM_015909
dbSNP: rs767134813
Type: single nucleotide variant
Location: chr2:15234708 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1995: 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

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.Arg1995Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
NBAS p.Arg1995Gly Conflicting classifications of pathogenicity ★ 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

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-arg1995ter (accessed [today's date]).

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