Is ARHGEF9 p.Phe245= (c.735C>T) pathogenic?

ARHGEF9 p.Phe245= (c.735C>T) is classified Likely benign in ARHGEF9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 8.

What condition is associated with ARHGEF9 p.Phe245= (c.735C>T)?

ARHGEF9 p.Phe245= (c.735C>T) is associated with developmental and epileptic encephalopathy, 8 (ClinVar).

How common is ARHGEF9 p.Phe245= (c.735C>T) in the general population?

ARHGEF9 p.Phe245= (c.735C>T) is absent from gnomAD v4.1 (gnomAD).

How is Hyperekplexia-epilepsy syndrome inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ARHGEF9 p.Phe245=

c.735C>T · rs2519751058 · VCV2756457

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

developmental and epileptic encephalopathy, 8

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 3.4	GERP 1.1, phastCons 1
Overall
CADD	9.645	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: ARHGEF9
Protein: p.Phe245=
Coding: c.735C>T
MANE Select: NM_001353921
dbSNP: rs2519751058
Type: single nucleotide variant
Location: chrX:63678420 (GRCh38)
Structure: AlphaFold pLDDT 80.79 · 1 PDB
Residue 245: the dh domain

Full ARHGEF9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperekplexia-epilepsy syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Neonatal

Similar variants

ARHGEF9 c.582+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARHGEF9 p.Arg111Gln Pathogenic/Likely pathogenic ★★ same condition
ARHGEF9 p.Arg296Ter Pathogenic ★★ same condition
ARHGEF9 p.Arg297His Pathogenic/Likely pathogenic ★★ same condition
ARHGEF9 p.Arg345Trp Pathogenic/Likely pathogenic ★★ same condition
ARHGEF9 p.Gln259Ter Pathogenic ★★ same condition
ARHGEF9 p.Glu186Lys Pathogenic/Likely pathogenic ★★ same condition
ARHGEF9 p.Trp423Ter Pathogenic ★★ 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/arhgef9-p-phe245 (accessed [today's date]).

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