Is ARHGEF7 p.Ser266Phe (c.797C>T) pathogenic?

ARHGEF7 p.Ser266Phe (c.797C>T) is classified Uncertain significance in ARHGEF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: ambiguous (0.4979); Absent from gnomAD v4.1.

How common is ARHGEF7 p.Ser266Phe (c.797C>T) in the general population?

ARHGEF7 p.Ser266Phe (c.797C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGEF7 p.Ser266Phe (c.797C>T)?

AlphaMissense predicts ambiguous (score 0.4979) — an in-silico prediction, not a clinical call.

ARHGEF7 p.Ser266Phe

c.797C>T · VCV4143092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4979	ambiguous
REVEL	0.298	indeterminate
SaProt	LLR -6.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 81 kb · p 2.6e-07 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S287F vs ClinVar S266F) — verify the residue.

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: ARHGEF7
Protein: p.Ser266Phe
Coding: c.797C>T
MANE Select: NM_001354046
Type: single nucleotide variant
Location: chr13:111243909 (GRCh38)
Gene constraint: LOEUF 0.53 · pLI 0.78 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.31 · 4 PDB

Full ARHGEF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PAK3 p.Arg100Ter Pathogenic/Likely pathogenic ★★ same type
PAK3 p.Arg436Ter Pathogenic/Likely pathogenic ★★ same type
PAK3 p.Glu356Ter Pathogenic/Likely pathogenic ★★ same type
PAK3 c.830+6T>A Uncertain significance ★★ same type
PAK3 p.Ala490Thr Uncertain significance ★★ ⚠ same type
PAK3 p.Arg493Cys Uncertain significance ★★ ⚠ same type
PAK3 p.Arg498Cys Uncertain significance ★★ ⚠ same type
PAK3 p.Asn185Thr Uncertain significance ★★ ⚠ 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/arhgef7-p-ser266phe (accessed [today's date]).

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