Is FGD1 p.Val718= (c.2154G>A) pathogenic?

FGD1 p.Val718= (c.2154G>A) is classified Uncertain significance in FGD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-19). Absent from gnomAD v4.1; Associated with Aarskog-Scott syndrome, X-linked.

What condition is associated with FGD1 p.Val718= (c.2154G>A)?

FGD1 p.Val718= (c.2154G>A) is associated with Aarskog-Scott syndrome, X-linked (ClinVar).

How common is FGD1 p.Val718= (c.2154G>A) in the general population?

FGD1 p.Val718= (c.2154G>A) is absent from gnomAD v4.1 (gnomAD).

FGD1 p.Val718=

c.2154G>A · rs2522692247 · VCV2441410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Aarskog-Scott syndrome, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP 2.1, phastCons 1
Overall
CADD	11.16	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: FGD1
Protein: p.Val718=
Coding: c.2154G>A
MANE Select: NM_004463
dbSNP: rs2522692247
Type: single nucleotide variant
Location: chrX:54449263 (GRCh38)
Structure: AlphaFold pLDDT 66.18
Residue 718: the 'disordered' region

Full FGD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Aarskog-Scott syndrome, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGD1 p.Val718Met Uncertain significance ★ ⚠ same residue
FGD1 p.Arg193Ter Pathogenic/Likely pathogenic ★★ same condition
FGD1 p.Arg519Cys Likely pathogenic ★★ same condition
FGD1 p.Arg522His Pathogenic/Likely pathogenic ★★ same condition
FGD1 p.Arg610Gln Pathogenic/Likely pathogenic ★★ same condition
FGD1 p.Arg656Ter Pathogenic ★★ same condition
FGD1 p.Arg910Ter Pathogenic/Likely pathogenic ★★ same condition
FGD1 p.Arg408Trp 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/fgd1-p-val718 (accessed [today's date]).

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