NR2F2 p.Ser278=
c.834G>A · rs199886454 · VCV413760
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.07%, sas)
Conditions
1
congenital heart defects, multiple types, 4
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 -0.46 | GERP -3.9, phastCons 0.002 |
| Overall | ||
| CADD | 8.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.07%
South Asian · 975/91,084 alleles
Filtering AF
1.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.992%
Overall
0.0713%
1,151/1,613,970 alleles · low-frequency
exomes 1,048/1,461,646 · genomes 103/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.07% | 93 |
| Remaining individualsnot grpmax-eligible | 0.106% | 947 |
| Middle Eastern | 0.0825% | 1,212 |
| Admixed American | 0.0566% | 1,765 |
| African / African-American | 0.00799% | 12,509 |
| Finnishnot grpmax-eligible | 0.00626% | 15,969 |
| European (non-Finnish) | 0.00508% | 19,667 |
| East Asian | 0.00223% | 44,864 |
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.Ser278=
- Coding
- c.834G>A
- MANE Select
- NM_021005
- dbSNP
- rs199886454
- Type
- single nucleotide variant
- Location
- chr15:96334467 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.94 · 1 PDB
- Residue 278
- the nr lbd domain; the 'interaction with zfpm2' region
Similar variants
- NR2F2 p.Ser341Tyr Pathogenic/Likely pathogenic ★★ same condition
- NR2F2 p.Trp249Ter Pathogenic/Likely pathogenic ★★ same condition
- NR2F2 p.Ala2Ser Uncertain significance ★★ ⚠ same condition
- NR2F2 p.Gly180Arg Uncertain significance ★★ ⚠ same condition
- NR2F2 p.Gly361Arg Uncertain significance ★★ ⚠ same condition
- NR2F2 p.His90Arg Uncertain significance ★★ ⚠ same condition
- NR2F2 p.Pro32Arg Uncertain significance ★★ ⚠ same condition
- NR2F2 p.Thr358Met 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-ser278 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown