Is FOXP2 p.Glu577= (c.1731A>G) pathogenic?

FOXP2 p.Glu577= (c.1731A>G) is classified Likely benign in FOXP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-28). Very rare (popmax 0.00134%, afr); Associated with FOXP2-related disorder.

What condition is associated with FOXP2 p.Glu577= (c.1731A>G)?

FOXP2 p.Glu577= (c.1731A>G) is associated with FOXP2-related disorder (ClinVar).

How common is FOXP2 p.Glu577= (c.1731A>G) in the general population?

FOXP2 p.Glu577= (c.1731A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

FOXP2 p.Glu577=

c.1731A>G · rs1806905090 · VCV3045396

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

FOXP2-related disorder

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 3.7	GERP -2, phastCons 1
Overall
CADD	9.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,862 alleles

Overall 0.000124% 2/1,612,830 alleles · very rare exomes 1/1,460,726 · genomes 1/152,104 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,862
European (non-Finnish)	8.48e-05%	1,179,216

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.Glu577=
Coding: c.1731A>G
MANE Select: NM_014491
dbSNP: rs1806905090
Type: single nucleotide variant
Location: chr7:114662148 (GRCh38)
Gene constraint: LOEUF 0.157 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.82 · 2 PDB
Residue 577: a DNA-binding region; an α-helix

Full FOXP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FOXP2-related disorder

Similar variants

FOXP2 p.Arg564Ter Pathogenic ★★ same condition
FOXP2 p.Ser42Cys Uncertain significance ★★ ⚠ same condition
FOXP2 p.Gln320Ter Likely pathogenic ★ same condition
FOXP2 c.258+36151T>G Uncertain significance ★ same condition
FOXP2 p.Arg583Gln Uncertain significance ★ ⚠ same condition
FOXP2 p.Glu643Lys Uncertain significance ★ ⚠ same condition
FOXP2 p.His333Arg Uncertain significance ★ ⚠ same condition
FOXP2 p.Leu638Pro 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/foxp2-p-glu577 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown