Is NPR3 p.Val369= (c.1107C>T) pathogenic?

NPR3 p.Val369= (c.1107C>T) is classified Likely benign in NPR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-26). Very rare (popmax 0.00134%, afr).

How common is NPR3 p.Val369= (c.1107C>T) in the general population?

NPR3 p.Val369= (c.1107C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

NPR3 p.Val369=

c.1107C>T · rs1442385834 · VCV2807412

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 0.085	GERP 0.025, phastCons 0.33
Overall
CADD	6.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,874 alleles

Overall 6.88e-05% 1/1,454,542 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: NPR3
Protein: p.Val369=
Coding: c.1107C>T
MANE Select: NM_001077350 · reported on NM_001204375
dbSNP: rs1442385834
Type: single nucleotide variant
Location: chr5:32774755 (GRCh38)
Structure: AlphaFold pLDDT 66.63 · 10 PDB

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

Similar variants

NPR3 p.Val369Ala Uncertain significance ★★ ⚠ same residue
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
NPR3 p.Thr428Ser 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-val369 (accessed [today's date]).

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