Is NBAS p.Arg2106fs (c.6312del) pathogenic?

NBAS p.Arg2106fs (c.6312del) is classified Pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-05). Very rare (popmax 8.47e-05%, nfe).

How common is NBAS p.Arg2106fs (c.6312del) in the general population?

NBAS p.Arg2106fs (c.6312del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

NBAS p.Arg2106fs

c.6312del · rs1343339242 · VCV2022534

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 48 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP -0.12, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,052 alleles

Overall 6.19e-05% 1/1,614,260 alleles · very rare exomes 1/1,461,882 · genomes 0/152,378 · 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.Arg2106fs
Coding: c.6312del
MANE Select: NM_015909
dbSNP: rs1343339242
Type: Deletion
Location: chr2:15218893 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 2106: 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

Similar variants

NBAS p.Arg2106Cys Uncertain significance ★★ ⚠ same residue
NBAS p.Arg2106His Uncertain significance ★★ same residue
NBAS p.Arg2106Gly Uncertain significance ★ ⚠ same residue
NBAS p.Arg2106Leu Uncertain significance ★ same residue
NBAS p.Arg2106= Likely benign ★ same residue
NBAS p.Asp2149_Ile2150insTer Pathogenic/Likely pathogenic ★★ same type
NBAS p.Cys1112fs Pathogenic ★★ same type
NBAS p.Gln2232fs Pathogenic/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-arg2106fs (accessed [today's date]).

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