Is NOD2 p.Pro765Arg (c.2294C>G) pathogenic?

NOD2 p.Pro765Arg (c.2294C>G) is classified Uncertain significance in NOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-01). AlphaMissense: likely benign (0.2353); Absent from gnomAD v4.1; Associated with Regional enteritis.

What condition is associated with NOD2 p.Pro765Arg (c.2294C>G)?

NOD2 p.Pro765Arg (c.2294C>G) is associated with Regional enteritis, Blau syndrome (ClinVar).

How common is NOD2 p.Pro765Arg (c.2294C>G) in the general population?

NOD2 p.Pro765Arg (c.2294C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOD2 p.Pro765Arg (c.2294C>G)?

AlphaMissense predicts likely benign (score 0.2353) — an in-silico prediction, not a clinical call.

NOD2 p.Pro765Arg

c.2294C>G · rs1964571054 · VCV837712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2353 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Regional enteritis

Computational evidence

Protein change
AlphaMissense	0.2353	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -10.69	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -0.57, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 20 kb · p 0.41 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P792R vs ClinVar P765R) — verify the residue.

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: NOD2
Protein: p.Pro765Arg
Coding: c.2294C>G
MANE Select: NM_001370466
dbSNP: rs1964571054
Type: single nucleotide variant
Location: chr16:50712286 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76

Full NOD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Regional enteritis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Blau syndrome

Similar variants

NOD2 p.Pro765= Likely benign ★★ same residue
NOD2 p.Arg307Gln Pathogenic ★★ ⚠ same condition
NOD2 p.Arg307Trp Pathogenic ★★ ⚠ same condition
NOD2 p.Arg560Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
NOD2 p.Met486Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
NOD2 c.2550-2A>G Uncertain significance ★★ same condition
NOD2 c.2717+2T>A Uncertain significance ★★ same condition
NOD2 c.2885+6G>T 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/nod2-p-pro765arg (accessed [today's date]).

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