Is NPR2 p.Val657fs (c.1968dup) pathogenic?

NPR2 p.Val657fs (c.1968dup) is classified Likely pathogenic in NPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-26). No gnomAD frequency available for this variant.

How common is NPR2 p.Val657fs (c.1968dup) in the general population?

NPR2 p.Val657fs (c.1968dup) is no gnomAD frequency available for this variant (gnomAD).

NPR2 p.Val657fs

c.1968dup · rs1554673888 · VCV422550

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

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 13 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1

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: NPR2
Protein: p.Val657fs
Coding: c.1968dup
MANE Select: NM_003995
dbSNP: rs1554673888
Type: Duplication
Location: chr9:35805587 (GRCh38)
Gene constraint: LOEUF 0.517 · pLI 0.45 (gnomAD)
Structure: AlphaFold pLDDT 84.00
Residue 657: the protein kinase domain

Full NPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NPR2 p.Arg828fs Pathogenic ★ same type
NPR2 p.Gly228fs Likely pathogenic ★ same type
NPR2 p.Met913fs Pathogenic ★ same type
NPR2 p.Phe1015delinsProArgTer Uncertain significance ★ same type
NPR2 c.1710+16_1710+19dup Likely benign ★ same type
NPR2 p.His948fs 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/npr2-p-val657fs (accessed [today's date]).

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