FOXP2 p.Ala259=
c.777T>A · VCV3371985
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000594%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.98 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.56 | gain · loss 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 22.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000594%
European (non-Finnish) · 7/1,179,368 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000434%
7/1,613,244 alleles · very rare
exomes 7/1,460,998 · genomes 0/152,246 · joint denominator
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.Ala259=
- Coding
- c.777T>A
- MANE Select
- NM_014491
- Type
- single nucleotide variant
- Location
- chr7:114642411 (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 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-ala259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown