Is NR2F2 p.Pro368Arg (c.1103C>G) pathogenic?

NR2F2 p.Pro368Arg (c.1103C>G) is classified Uncertain significance in NR2F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1; Associated with NR2F2-related disorder.

What condition is associated with NR2F2 p.Pro368Arg (c.1103C>G)?

NR2F2 p.Pro368Arg (c.1103C>G) is associated with NR2F2-related disorder (ClinVar).

How common is NR2F2 p.Pro368Arg (c.1103C>G) in the general population?

NR2F2 p.Pro368Arg (c.1103C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NR2F2 p.Pro368Arg (c.1103C>G)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

NR2F2 p.Pro368Arg

c.1103C>G · rs2505780179 · VCV2631321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

NR2F2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -17.17	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 7.6	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	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Pro368Arg
Coding: c.1103C>G
MANE Select: NM_021005
dbSNP: rs2505780179
Type: single nucleotide variant
Location: chr15:96337480 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 1 PDB
Residue 368: the nr lbd domain; an α-helix; 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

NR2F2-related disorder

Similar variants

NR2F2 p.Trp249Ter Pathogenic/Likely pathogenic ★★ same condition
NR2F2 c.443-2A>T Pathogenic ★ same condition
NR2F2 p.Gly88Asp Likely pathogenic ★ same condition
NR2F2 p.Ser86Leu Likely pathogenic ★ same condition
NR2F2 p.Gly58Arg Uncertain significance ★ ⚠ same condition
NR2F2 p.Pro66Leu Uncertain significance ★ ⚠ same condition
NR2F2 p.Trp8Ter Likely pathogenic same condition
NR2F2 p.Arg105Ser 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-pro368arg (accessed [today's date]).

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