Is NR2F2 p.Pro37Arg (c.110C>G) pathogenic?

NR2F2 p.Pro37Arg (c.110C>G) is classified Uncertain significance in NR2F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.1501); Very rare (popmax 0.00274%, amr); Associated with Inborn genetic diseases.

What condition is associated with NR2F2 p.Pro37Arg (c.110C>G)?

NR2F2 p.Pro37Arg (c.110C>G) is associated with Inborn genetic diseases (ClinVar).

How common is NR2F2 p.Pro37Arg (c.110C>G) in the general population?

NR2F2 p.Pro37Arg (c.110C>G) is very rare (popmax 0.00274%, amr) (gnomAD).

What do computational predictors say about NR2F2 p.Pro37Arg (c.110C>G)?

AlphaMissense predicts likely benign (score 0.1501) — an in-silico prediction, not a clinical call.

NR2F2 p.Pro37Arg

c.110C>G · VCV3921642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1501 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00274%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1501	likely benign
REVEL	0.517	indeterminate
SaProt	LLR -12.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 0.48, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 bp · p 0.79 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.00274% Admixed American · 1/36,502 alleles

Filtering AF 0.000748% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000585%

Overall 0.00106% 15/1,418,720 alleles · very rare exomes 13/1,267,116 · genomes 2/151,604 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00274%	36,502
European (non-Finnish)	0.00129%	77,546

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: NR2F2
Protein: p.Pro37Arg
Coding: c.110C>G
MANE Select: NM_021005
Type: single nucleotide variant
Location: chr15:96332215 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 1 PDB
Residue 37: the 'disordered' 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.Pro37Leu Uncertain significance ★ ⚠ same residue
NR2F2 p.Gly180Arg Uncertain significance ★★ ⚠ same condition
NR2F2 p.Lys137Arg Uncertain significance ★★ ⚠ same condition
NR2F2 p.Arg366Pro Pathogenic ★ 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

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-pro37arg (accessed [today's date]).

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