FOXP1 p.Pro421=
c.1263C>G · rs746264001 · VCV1763563
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.023 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP -0.62, phastCons 1 |
| Overall | ||
| CADD | 8.868 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,026 alleles
Overall
0.000124%
2/1,614,200 alleles · very rare
exomes 2/1,461,876 · genomes 0/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,026 |
| European (non-Finnish) | 8.47e-05% | 1,180,034 |
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
- FOXP1
- Protein
- p.Pro421=
- Coding
- c.1263C>G
- MANE Select
- NM_001349338
- dbSNP
- rs746264001
- Type
- single nucleotide variant
- Location
- chr3:70977913 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.27 · 1 PDB
- Residue 421
- the 'disordered' region
Similar variants
- FOXP1 c.1146+1G>A Pathogenic/Likely pathogenic ★★ same condition
- FOXP1 c.1652+5G>C Pathogenic/Likely pathogenic ★★ same condition
- FOXP1 p.Arg544Gln Likely pathogenic ★★ same condition
- FOXP1 p.Gln177Ter Pathogenic ★★ same condition
- FOXP1 p.Leu517Phe Pathogenic ★★ same condition
- FOXP1 p.Lys393Ter Pathogenic ★★ same condition
- FOXP1 p.Phe502Leu Pathogenic/Likely pathogenic ★★ same condition
- FOXP1 p.Val513Ala Pathogenic/Likely pathogenic ★★ 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/foxp1-p-pro421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown