Is NYNRIN p.Val287= (c.861C>G) pathogenic?

NYNRIN p.Val287= (c.861C>G) is classified Uncertain significance in NYNRIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). Very rare (popmax 0.00135%, afr); Associated with Predisposition to Wilms tumor.

What condition is associated with NYNRIN p.Val287= (c.861C>G)?

NYNRIN p.Val287= (c.861C>G) is associated with Predisposition to Wilms tumor (ClinVar).

How common is NYNRIN p.Val287= (c.861C>G) in the general population?

NYNRIN p.Val287= (c.861C>G) is very rare (popmax 0.00135%, afr) (gnomAD).

NYNRIN p.Val287=

c.861C>G · VCV3602681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

Predisposition to Wilms tumor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.47	acceptor loss, 3 bp away · masked 0 · deltas
Pangolin	Δ0.24	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.8	GERP -4.3
Overall
CADD	0.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/74,264 alleles

Overall 0.000125% 2/1,595,666 alleles · very rare exomes 1/1,443,460 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	74,264
European (non-Finnish)	8.53e-05%	1,171,746

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: NYNRIN
Protein: p.Val287=
Coding: c.861C>G
MANE Select: NM_025081
Type: single nucleotide variant
Location: chr14:24408655 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.04

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

Disease context

Predisposition to Wilms tumor

Similar variants

NYNRIN p.Ala555Asp Uncertain significance ★★ ⚠ same condition
NYNRIN p.Arg1433Trp Uncertain significance ★★ ⚠ same condition
NYNRIN p.Asp1106Val Uncertain significance ★★ ⚠ same condition
NYNRIN p.Gly1452Arg Uncertain significance ★★ ⚠ same condition
NYNRIN p.Leu1713Pro Uncertain significance ★★ ⚠ same condition
NYNRIN p.Lys259Met Uncertain significance ★★ ⚠ same condition
NYNRIN p.Lys679Gln Uncertain significance ★★ ⚠ same condition
NYNRIN p.Met1786Val 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/nynrin-p-val287 (accessed [today's date]).

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