Is NPR2 p.Phe475Val (c.1423T>G) pathogenic?

NPR2 p.Phe475Val (c.1423T>G) is classified Uncertain significance in NPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.3194); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NPR2 p.Phe475Val (c.1423T>G)?

NPR2 p.Phe475Val (c.1423T>G) is associated with Inborn genetic diseases (ClinVar).

How common is NPR2 p.Phe475Val (c.1423T>G) in the general population?

NPR2 p.Phe475Val (c.1423T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NPR2 p.Phe475Val (c.1423T>G)?

AlphaMissense predicts likely benign (score 0.3194) — an in-silico prediction, not a clinical call.

NPR2 p.Phe475Val

c.1423T>G · rs2491047771 · VCV2481593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3194 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3194	likely benign
REVEL	0.485	indeterminate
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NPR2
Protein: p.Phe475Val
Coding: c.1423T>G
MANE Select: NM_003995
dbSNP: rs2491047771
Type: single nucleotide variant
Location: chr9:35801141 (GRCh38)
Gene constraint: LOEUF 0.517 · pLI 0.45 (gnomAD)
Structure: AlphaFold pLDDT 84.00

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPR2 p.Ala190Gly Uncertain significance ★★ ⚠ same condition
NPR2 p.Ala22Val Uncertain significance ★★ ⚠ same condition
NPR2 p.Arg268His Uncertain significance ★★ ⚠ same condition
NPR2 p.Arg272Gln Uncertain significance ★★ ⚠ same condition
NPR2 p.Arg363Gln Uncertain significance ★★ ⚠ same condition
NPR2 p.Arg58Pro Uncertain significance ★★ ⚠ same condition
NPR2 p.Arg65Trp Uncertain significance ★★ ⚠ same condition
NPR2 p.Arg745Gln Uncertain significance ★★ ⚠ 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/npr2-p-phe475val (accessed [today's date]).

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