Is NPR3 p.Ser296= (c.888C>A) pathogenic?

NPR3 p.Ser296= (c.888C>A) is classified Likely benign in NPR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Very rare (popmax 0.00533%, afr); Associated with NPR3-related disorder.

What condition is associated with NPR3 p.Ser296= (c.888C>A)?

NPR3 p.Ser296= (c.888C>A) is associated with NPR3-related disorder (ClinVar).

How common is NPR3 p.Ser296= (c.888C>A) in the general population?

NPR3 p.Ser296= (c.888C>A) is very rare (popmax 0.00533%, afr) (gnomAD).

NPR3 p.Ser296=

c.888C>A · rs1316577485 · VCV3040450

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Conditions

NPR3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP 0.72, phastCons 1
Overall
CADD	7.858	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,026 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000411% 6/1,461,606 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,756
South Asian	0.0011%	91,080
European (non-Finnish)	8.48e-05%	1,179,852

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: NPR3
Protein: p.Ser296=
Coding: c.888C>A
MANE Select: NM_001077350 · reported on NM_001204375
dbSNP: rs1316577485
Type: single nucleotide variant
Location: chr5:32724816 (GRCh38)
Structure: AlphaFold pLDDT 66.63 · 10 PDB
Residue 296: an α-helix

Full NPR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NPR3-related disorder

Similar variants

NPR3 c.50-14043G>A Benign same condition
NPR3 p.Leu6= Benign same condition
NPR3 p.Ala274Val Uncertain significance ★★ same type
NPR3 p.Arg530Gln Uncertain significance ★★ ⚠ same type
NPR3 p.Asp306Asn Uncertain significance ★★ ⚠ same type
NPR3 p.Glu480Gly Uncertain significance ★★ ⚠ same type
NPR3 p.Gly453Asp Uncertain significance ★★ ⚠ same type
NPR3 p.His373Arg Uncertain significance ★★ ⚠ 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/npr3-p-ser296 (accessed [today's date]).

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