FOXP2 p.Pro660=
c.1980G>A · VCV3389079
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00322%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -12 |
| Overall | ||
| CADD | 0.212 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00322%
European (non-Finnish) · 38/1,179,632 alleles
Filtering AF
0.00239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00254%
41/1,613,316 alleles · very rare
exomes 40/1,461,248 · genomes 1/152,068 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00322% | 31,043 |
| African / African-American | 0.00267% | 37,428 |
| South Asian | 0.0011% | 91,076 |
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.Pro660=
- Coding
- c.1980G>A
- MANE Select
- NM_014491
- Type
- single nucleotide variant
- Location
- chr7:114664413 (GRCh38)
- Gene constraint
- LOEUF 0.157 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.82 · 2 PDB
- Residue 660
- the 'disordered' region
Similar variants
- FOXP2 p.Arg328Ter Pathogenic ★★ same type
- FOXP2 p.Arg376Ter Pathogenic ★★ same type
- FOXP2 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same type
- FOXP2 p.Arg478Ter Pathogenic ★★ same type
- FOXP2 p.Arg553His Pathogenic/Likely pathogenic ★★ same type
- FOXP2 p.Arg564Ter Pathogenic ★★ same type
- FOXP2 p.Gln168Ter Pathogenic/Likely pathogenic ★★ same type
- FOXP2 p.Gln187Ter 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/foxp2-p-pro660 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown