Is NRP1 p.Pro682= (c.2046C>G) pathogenic?

NRP1 p.Pro682= (c.2046C>G) is classified Likely benign in NRP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-06). Ultra-rare (popmax 0.0133%, amr); Associated with NRP1-related disorder.

What condition is associated with NRP1 p.Pro682= (c.2046C>G)?

NRP1 p.Pro682= (c.2046C>G) is associated with NRP1-related disorder (ClinVar).

How common is NRP1 p.Pro682= (c.2046C>G) in the general population?

NRP1 p.Pro682= (c.2046C>G) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

NRP1 p.Pro682=

c.2046C>G · VCV3351383

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

NRP1-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 -1.1	GERP -4.1
Overall
CADD	5.628	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,958 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000558% 9/1,613,506 alleles · ultra-rare exomes 7/1,461,414 · genomes 2/152,092 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,495
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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: NRP1
Protein: p.Pro682=
Coding: c.2046C>G
MANE Select: NM_003873
Type: single nucleotide variant
Location: chr10:33192297 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.83 · 27 PDB
Residue 682: the mam domain; a β-strand

Full NRP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NRP1-related disorder

Similar variants

NRP1 p.Ala17Ser Uncertain significance ★ ⚠ same condition
NRP1 p.Ala537Thr Uncertain significance ★ ⚠ same condition
NRP1 p.Arg305His Uncertain significance ★ ⚠ same condition
NRP1 p.Arg405Gln Uncertain significance ★ ⚠ same condition
NRP1 p.Glu312Asp Uncertain significance ★ ⚠ same condition
NRP1 p.Gly202Ala Uncertain significance ★ ⚠ same condition
NRP1 p.Gly43Ser Uncertain significance ★ same condition
NRP1 p.Gly542= 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/nrp1-p-pro682 (accessed [today's date]).

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