Is NBAS p.Val84fs (c.248_249dup) pathogenic?

NBAS p.Val84fs (c.248249dup) is classified Pathogenic in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Very rare (popmax 0.005%, amr).

How common is NBAS p.Val84fs (c.248_249dup) in the general population?

NBAS p.Val84fs (c.248_249dup) is very rare (popmax 0.005%, amr) (gnomAD).

NBAS p.Val84fs

c.248_249dup · rs760730197 · VCV2881213

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 4 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP -0.72, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,984 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,732 alleles · very rare

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.Val84fs
Coding: c.248_249dup
MANE Select: NM_015909
dbSNP: rs760730197
Type: Duplication
Location: chr2:15554098 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 84: the 'interaction with use1' region

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

Similar variants

NBAS p.Gln1282fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Leu1231fs Pathogenic ★★ same type
NBAS p.Leu1962fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Leu864fs Pathogenic/Likely pathogenic ★★ same type
NBAS p.Thr119fs Pathogenic ★★ same type
NBAS p.Tyr142Ter Pathogenic/Likely pathogenic ★★ same type
NBAS c.3072-19dup Benign/Likely benign ★★ same type
NBAS c.3258-5dup Benign/Likely benign ★★ 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-val84fs (accessed [today's date]).

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