Is NBAS p.Arg694Ter (c.2080C>T) pathogenic?

NBAS p.Arg694Ter (c.2080C>T) is classified Pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-26). Very rare (popmax 0.00212%, nfe).

How common is NBAS p.Arg694Ter (c.2080C>T) in the general population?

NBAS p.Arg694Ter (c.2080C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

NBAS p.Arg694Ter

c.2080C>T · rs1449768284 · VCV3014184

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

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 19 of 52
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Pangolin	Δ0.25	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	44.0	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 0.00212% European (non-Finnish) · 25/1,178,790 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00155% 25/1,612,414 alleles · very rare exomes 24/1,460,264 · genomes 1/152,150 · joint denominator

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.Arg694Ter
Coding: c.2080C>T
MANE Select: NM_015909
dbSNP: rs1449768284
Type: single nucleotide variant
Location: chr2:15467346 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 694: 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

Similar variants

NBAS p.Arg694Gln Uncertain significance ★ ⚠ same residue
NBAS c.1726-2A>G Likely pathogenic ★★ same type
NBAS c.173-2A>G Likely pathogenic ★★ same type
NBAS c.209+2T>G Pathogenic/Likely pathogenic ★★ same type
NBAS c.2423+404G>C Likely pathogenic ★★ same type
NBAS c.335+1G>C Pathogenic/Likely pathogenic ★★ same type
NBAS c.4461+2T>C Likely pathogenic ★★ same type
NBAS c.4583-2A>G Likely pathogenic ★★ same type

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-arg694ter (accessed [today's date]).

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