Is NR2F1 p.Pro20Ser (c.58C>T) pathogenic?

NR2F1 p.Pro20Ser (c.58C>T) is classified Uncertain significance in NR2F1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.0662); No allele count reported in gnomAD v4.1 (AN 1,022,792).

How common is NR2F1 p.Pro20Ser (c.58C>T) in the general population?

NR2F1 p.Pro20Ser (c.58C>T) is no allele count reported in gnomAD v4.1 (AN 1,022,792) (gnomAD).

What do computational predictors say about NR2F1 p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

NR2F1 p.Pro20Ser

c.58C>T · rs2480800803 · VCV2129461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,022,792)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP -1.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 241 bp · p 0.11 · regional, not allelic
Overall
CADD	18.47	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 1,022,792). 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: NR2F1
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_005654
dbSNP: rs2480800803
Type: single nucleotide variant
Location: chr5:93585081 (GRCh38)
Gene constraint: LOEUF 0.133 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 76.81 · 1 PDB
Residue 20: the 'disordered' region

Full NR2F1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NR2F1 p.Pro20= Likely benign ★★ same residue
NR2F1 p.Pro20His Uncertain significance ★ ⚠ same residue
NR2F1 p.Pro20Leu Uncertain significance ★ ⚠ same residue
NR2F1 c.463+1G>A Likely pathogenic ★★ same type
NR2F1 p.Arg366Cys Likely pathogenic ★★ same type
NR2F1 p.Cys106Tyr Pathogenic/Likely pathogenic ★★ same type
NR2F1 p.Cys122Tyr Likely pathogenic ★★ same type
NR2F1 p.Cys128Arg Likely pathogenic ★★ same type

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/nr2f1-p-pro20ser (accessed [today's date]).

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