Is FOXL2 p.Lys124Glu (c.370A>G) pathogenic?

FOXL2 p.Lys124Glu (c.370A>G) is classified Likely pathogenic in FOXL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-26). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is FOXL2 p.Lys124Glu (c.370A>G) in the general population?

FOXL2 p.Lys124Glu (c.370A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXL2 p.Lys124Glu (c.370A>G)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

FOXL2 p.Lys124Glu

c.370A>G · rs2107744566 · VCV2734576

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 8% in FOXL2
REVEL	0.971	strongly pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 5.1, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 283 bp · p 1.2e-10 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: FOXL2
Protein: p.Lys124Glu
Coding: c.370A>G
MANE Select: NM_023067
dbSNP: rs2107744566
Type: single nucleotide variant
Location: chr3:138946353 (GRCh38)
Gene constraint: LOEUF 1.913 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.89 · 2 PDB
Residue 124: a DNA-binding region

Full FOXL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FOXL2 p.Lys124fs Pathogenic ★ same residue
FOXL2 p.Arg349Gly Likely pathogenic ★★ ⚠ same type
FOXL2 p.Gln196Ter Pathogenic ★★ same type
FOXL2 p.Gln219Ter Pathogenic ★★ same type
FOXL2 p.Leu75Phe Pathogenic ★★ same type
FOXL2 p.Met65Ile Likely pathogenic ★★ same type
FOXL2 p.Met65Val Pathogenic/Likely pathogenic ★★ same type
FOXL2 p.Ser107Gly Likely 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/foxl2-p-lys124glu (accessed [today's date]).

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