Is NR2F2 p.Pro16= (c.48C>T) pathogenic?

NR2F2 p.Pro16= (c.48C>T) is classified Likely benign in NR2F2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-28). Very rare (popmax 0.00194%, sas); Associated with NR2F2-related disorder.

What condition is associated with NR2F2 p.Pro16= (c.48C>T)?

NR2F2 p.Pro16= (c.48C>T) is associated with NR2F2-related disorder (ClinVar).

How common is NR2F2 p.Pro16= (c.48C>T) in the general population?

NR2F2 p.Pro16= (c.48C>T) is very rare (popmax 0.00194%, sas) (gnomAD).

NR2F2 p.Pro16=

c.48C>T · rs1899165403 · VCV3051780

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00194%, sas)

Conditions

NR2F2-related disorder

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 1.3	GERP -0.56, phastCons 1
Overall
CADD	14.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00194% South Asian · 1/51,622 alleles

Filtering AF 7.6e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.000295% 4/1,354,786 alleles · very rare exomes 3/1,203,004 · genomes 1/151,782 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00194%	51,622
European (non-Finnish)	0.000285%	351,247

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.Pro16=
Coding: c.48C>T
MANE Select: NM_021005
dbSNP: rs1899165403
Type: single nucleotide variant
Location: chr15:96332153 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 1 PDB
Residue 16: the 'disordered' region

Full NR2F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NR2F2-related disorder

Similar variants

NR2F2 p.Pro16His Uncertain significance ★ ⚠ same residue
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.Pro368Arg Uncertain significance ★ ⚠ same condition
NR2F2 p.Pro66Leu 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-pro16 (accessed [today's date]).

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