Is NBAS p.Lys384fs (c.1151_1152del) pathogenic?

NBAS p.Lys384fs (c.11511152del) is classified Pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). Very rare (popmax 0.0011%, sas).

How common is NBAS p.Lys384fs (c.1151_1152del) in the general population?

NBAS p.Lys384fs (c.1151_1152del) is very rare (popmax 0.0011%, sas) (gnomAD).

NBAS p.Lys384fs

c.1151_1152del · rs1234886272 · VCV2106997

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 14 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 0.99, 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 0.0011% South Asian · 1/90,814 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,612,304 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,814
European (non-Finnish)	0.000254%	392,930

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.Lys384fs
Coding: c.1151_1152del
MANE Select: NM_015909
dbSNP: rs1234886272
Type: Deletion
Location: chr2:15475876 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 384: a UniProt-annotated variant site (in ilfs2; uncertain significance); the 'interaction with use1' region

Full NBAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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NBAS p.Cys1112fs Pathogenic ★★ same type
NBAS p.Gln2232fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Gln44fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Glu1092fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Ile984fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Leu1507fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Leu1726fs 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-lys384fs (accessed [today's date]).

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