Is NR2F2 p.Pro34Ser (c.100C>T) pathogenic?

NR2F2 p.Pro34Ser (c.100C>T) is classified Uncertain significance in NR2F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-27). AlphaMissense: likely benign (0.0579); No allele count reported in gnomAD v4.1 (AN 1,352,044); Associated with Inborn genetic diseases.

What condition is associated with NR2F2 p.Pro34Ser (c.100C>T)?

NR2F2 p.Pro34Ser (c.100C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NR2F2 p.Pro34Ser (c.100C>T) in the general population?

NR2F2 p.Pro34Ser (c.100C>T) is no allele count reported in gnomAD v4.1 (AN 1,352,044) (gnomAD).

What do computational predictors say about NR2F2 p.Pro34Ser (c.100C>T)?

AlphaMissense predicts likely benign (score 0.0579) — an in-silico prediction, not a clinical call.

NR2F2 p.Pro34Ser

c.100C>T · rs1899167460 · VCV2541489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0579 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,352,044)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0579	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP -0.51, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 bp · p 0.79 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,352,044). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NR2F2
Protein: p.Pro34Ser
Coding: c.100C>T
MANE Select: NM_021005
dbSNP: rs1899167460
Type: single nucleotide variant
Location: chr15:96332205 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 1 PDB
Residue 34: 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.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
NR2F2 p.Ala26Pro 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-pro34ser (accessed [today's date]).

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