Is FOXE3 p.Ala83= (c.249T>G) pathogenic?

FOXE3 p.Ala83= (c.249T>G) is classified Likely benign in FOXE3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with FOXE3 p.Ala83= (c.249T>G)?

FOXE3 p.Ala83= (c.249T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is FOXE3 p.Ala83= (c.249T>G) in the general population?

FOXE3 p.Ala83= (c.249T>G) is absent from gnomAD v4.1 (gnomAD).

FOXE3 p.Ala83=

c.249T>G · rs2124042180 · VCV2496953

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,012)

Conditions

Cardiovascular phenotype

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 0.092	GERP -3.9, phastCons 0.1
Overall
CADD	6.599	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,596,012). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FOXE3
Protein: p.Ala83=
Coding: c.249T>G
MANE Select: NM_012186
dbSNP: rs2124042180
Type: single nucleotide variant
Location: chr1:47416564 (GRCh38)
Gene constraint: LOEUF 1.935 · pLI 0.12 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.68
Residue 83: a DNA-binding region

Full FOXE3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FOXE3 p.Ala170Thr Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala245Thr Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala255Thr Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala257Ser Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala295Thr Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala44Glu Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala51Ser Uncertain significance ★★ ⚠ same condition
FOXE3 p.Arg113Pro 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/foxe3-p-ala83 (accessed [today's date]).

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