Is NEB p.Asp2000fs (c.5999dup) pathogenic?

NEB p.Asp2000fs (c.5999dup) is classified Likely pathogenic in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-02). No gnomAD frequency available for this variant; Associated with arthrogryposis multiplex congenita 6.

What condition is associated with NEB p.Asp2000fs (c.5999dup)?

NEB p.Asp2000fs (c.5999dup) is associated with arthrogryposis multiplex congenita 6 (ClinVar).

How common is NEB p.Asp2000fs (c.5999dup) in the general population?

NEB p.Asp2000fs (c.5999dup) is no gnomAD frequency available for this variant (gnomAD).

NEB p.Asp2000fs

c.5999dup · rs2552254255 · VCV2677080

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arthrogryposis multiplex congenita 6

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 47 of 182
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.18	GERP -3.9, phastCons 0.74

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NEB
Protein: p.Asp2000fs
Coding: c.5999dup
MANE Select: NM_001164508
dbSNP: rs2552254255
Type: Duplication
Location: chr2:151659140 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 2000: a UniProt-annotated variant site (in amc6)

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

Disease context

arthrogryposis multiplex congenita 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NEB c.12639+2dup Uncertain significance ★★★ same condition
NEB c.1470+2dup Likely pathogenic ★★ same condition
NEB p.Arg8186fs Pathogenic/Likely pathogenic ★★ same condition
NEB p.Asn2713fs Likely pathogenic ★★ same condition
NEB p.Asn7951fs Pathogenic/Likely pathogenic ★★ same condition
NEB p.Asn8001fs Pathogenic/Likely pathogenic ★★ same condition
NEB p.Asn8168fs Pathogenic/Likely pathogenic ★★ same condition
NEB p.Asp3676fs Pathogenic/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/neb-p-asp2000fs (accessed [today's date]).

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