Is FOXP2 p.Val388= (c.1164G>T) pathogenic?

FOXP2 p.Val388= (c.1164G>T) is classified Uncertain significance in FOXP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-06). Absent from gnomAD v4.1; Associated with lung adenocarcinoma.

What condition is associated with FOXP2 p.Val388= (c.1164G>T)?

FOXP2 p.Val388= (c.1164G>T) is associated with lung adenocarcinoma (ClinVar).

How common is FOXP2 p.Val388= (c.1164G>T) in the general population?

FOXP2 p.Val388= (c.1164G>T) is absent from gnomAD v4.1 (gnomAD).

FOXP2 p.Val388=

c.1164G>T · rs1806304987 · VCV2431182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

lung adenocarcinoma

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 -0.28	GERP -5.5, phastCons 0.014
Overall
CADD	1.597	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FOXP2
Protein: p.Val388=
Coding: c.1164G>T
MANE Select: NM_014491
dbSNP: rs1806304987
Type: single nucleotide variant
Location: chr7:114652272 (GRCh38)
Gene constraint: LOEUF 0.157 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.82 · 2 PDB
Residue 388: the foxp leucine zipper (zip) domain

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

Disease context

lung adenocarcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FOXP2 c.2003+1336G>C Uncertain significance ★ same condition
FOXP2 c.2003+4074C>A Uncertain significance ★ same condition
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

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-val388 (accessed [today's date]).

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