Is NRIP1 p.Pro259= (c.777T>C) pathogenic?

NRIP1 p.Pro259= (c.777T>C) is classified Likely benign in NRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Absent from gnomAD v4.1.

How common is NRIP1 p.Pro259= (c.777T>C) in the general population?

NRIP1 p.Pro259= (c.777T>C) is absent from gnomAD v4.1 (gnomAD).

NRIP1 p.Pro259=

c.777T>C · rs2516288053 · VCV1998079

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.19	GERP -3.9, phastCons 0.002
Overall
CADD	1.792	PHRED · no single calibrated threshold — expert panels disagree

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: NRIP1
Protein: p.Pro259=
Coding: c.777T>C
MANE Select: NM_003489
dbSNP: rs2516288053
Type: single nucleotide variant
Location: chr21:14967416 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 46.10 · 17 PDB
Residue 259: the 'interaction with znf366' region; the 'repression domain 1' region

Full NRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NRIP1 p.Pro259Leu Uncertain significance ★ ⚠ same residue
NRIP1 p.Ala1096Gly Uncertain significance ★★ ⚠ same type
NRIP1 p.Ala360Ser Uncertain significance ★★ ⚠ same type
NRIP1 p.Ala36Pro Uncertain significance ★★ ⚠ same type
NRIP1 p.Ala792Val Uncertain significance ★★ ⚠ same type
NRIP1 p.Arg1082Gly Uncertain significance ★★ ⚠ same type
NRIP1 p.Arg1122Gly Uncertain significance ★★ ⚠ same type
NRIP1 p.Arg98Trp 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/nrip1-p-pro259 (accessed [today's date]).

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