FOXP2 p.Arg477=
c.1431G>A · rs148518030 · VCV588953
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0733%, afr)
Conditions
2
Inborn genetic diseases
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 10 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 10.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0733%
African / African-American · 55/74,984 alleles
Filtering AF
0.0578%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0522%
Overall
0.00353%
57/1,613,774 alleles · ultra-rare
exomes 25/1,461,598 · genomes 32/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0733% | 1,363 |
| Admixed American | 0.00167% | 59,978 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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
- FOXP2
- Protein
- p.Arg477=
- Coding
- c.1431G>A
- MANE Select
- NM_014491
- dbSNP
- rs148518030
- Type
- single nucleotide variant
- Location
- chr7:114658230 (GRCh38)
- Gene constraint
- LOEUF 0.157 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.82 · 2 PDB
Similar variants
- FOXP2 p.Arg328Ter Pathogenic ★★ same condition
- FOXP2 p.Arg376Ter Pathogenic ★★ same condition
- FOXP2 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same condition
- FOXP2 p.Arg478Ter Pathogenic ★★ same condition
- FOXP2 p.Arg553His Pathogenic/Likely pathogenic ★★ same condition
- FOXP2 p.Arg564Ter Pathogenic ★★ same condition
- FOXP2 p.Gln168Ter Pathogenic/Likely pathogenic ★★ same condition
- FOXP2 p.Gln187Ter 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/foxp2-p-arg477 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown