Is NR2F2 p.Arg366Pro (c.1097G>C) pathogenic?

NR2F2 p.Arg366Pro (c.1097G>C) is classified Pathogenic in NR2F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-06). AlphaMissense: likely pathogenic (0.9991); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NR2F2 p.Arg366Pro (c.1097G>C)?

NR2F2 p.Arg366Pro (c.1097G>C) is associated with Inborn genetic diseases (ClinVar).

How common is NR2F2 p.Arg366Pro (c.1097G>C) in the general population?

NR2F2 p.Arg366Pro (c.1097G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NR2F2 p.Arg366Pro (c.1097G>C)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

NR2F2 p.Arg366Pro

c.1097G>C · rs1555447465 · VCV521133

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic ✓ concordant with ClinVar · top 8% in NR2F2
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -13.63	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 3,543 bp · p 6.1e-26 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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: NR2F2
Protein: p.Arg366Pro
Coding: c.1097G>C
MANE Select: NM_021005
dbSNP: rs1555447465
Type: single nucleotide variant
Location: chr15:96337474 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 1 PDB
Residue 366: the nr lbd domain; the 'interaction with zfpm2' region; the 'important for dimerization' region

Full NR2F2 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

NR2F2 p.Gly180Arg Uncertain significance ★★ ⚠ same condition
NR2F2 p.Lys137Arg Uncertain significance ★★ ⚠ same condition
NR2F2 p.Cys314Arg Likely pathogenic ★ same condition
NR2F2 p.Gln22Ter Pathogenic ★ same condition
NR2F2 p.Gln259Ter Pathogenic ★ same condition
NR2F2 p.Ala217Thr Uncertain significance ★ ⚠ same condition
NR2F2 p.Ala26Pro Uncertain significance ★ ⚠ same condition
NR2F2 p.Ala26Val 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/nr2f2-p-arg366pro (accessed [today's date]).

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