Variant: NM_005249.5(FOXG1):c.131A>C (p.His44Pro)

CA389474457

449126 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

UUID: afe54daf-e61f-4752-a1c8-8e90376e414f

Approved on: 2025-06-25

Published on: 2025-06-30

HGVS expressions

NM_005249.5:c.131A>C
NM_005249.5(FOXG1):c.131A>C (p.His44Pro)
NC_000014.9:g.28767410A>C
CM000676.2:g.28767410A>C
NC_000014.8:g.29236616A>C
CM000676.1:g.29236616A>C
NC_000014.7:g.28306367A>C
NG_009367.1:g.5330A>C
ENST00000706482.1:c.131A>C
ENST00000313071.7:c.131A>C
ENST00000313071.6:c.131A>C
NM_005249.4:c.131A>C

Likely Benign

• Met criteria codes: BP4 BS2_Supporting

• Not Met criteria codes: BS1 PS4 PM2

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for FOXG1 Version 4.1.0

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The highest population minor allele frequency of the p.His44Pro variant in FOXG1 in gnomAD v4.1 is 0.00002649 in the Non-Finnish European population (not sufficient to meet BS1 criteria). The p.His44Pro variant is observed in at least 1 unaffected individual (Internal database - Ambry Genetics) (BS2_Supporting). The computational predictor REVEL gives a score of 0.041, which is below the threshold of 0.290, evidence that does not predict a damaging effect on FOXG1 function (BP4). In summary, the p.His44Pro variant in FOXG1 is classified as likely benign based on the ACMG/AMP criteria (BS2_Supporting, BP4). (FOXG1 Specifications v.4.1; curation approved on [06/25/2025])

Met criteria codes

• BP4: The computational predictor REVEL gives a score of 0.041, which is below the threshold of 0.290, evidence that does not predict a damaging effect on FOXG1 function (BP4).
• BS2_Supporting: The p.His44Pro variant is observed in at least 1 unaffected individual (Internal database - Ambry Genetics) (BS2_Supporting).

Not Met criteria codes

• BS1: The highest population minor allele frequency of the p.His44Pro variant in FOXG1 in gnomAD v4.1 is 0.00002649 in the Non-Finnish European population (not sufficient to meet BS1 criteria).
• PS4: This variant is not rare and is present in gnomAD.
• PM2: gnomAD v4.1 - 28 alleles, MAF (ENF) 0.00002649