Is FGD1 p.Pro539= (c.1617G>A) pathogenic?

FGD1 p.Pro539= (c.1617G>A) is classified Benign/Likely benign in FGD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-11). Rare (popmax 0.641%, afr); Associated with Inborn genetic diseases.

What condition is associated with FGD1 p.Pro539= (c.1617G>A)?

FGD1 p.Pro539= (c.1617G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FGD1 p.Pro539= (c.1617G>A) in the general population?

FGD1 p.Pro539= (c.1617G>A) is rare (popmax 0.641%, afr) (gnomAD).

FGD1 p.Pro539=

c.1617G>A · rs151184308 · VCV198808

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.641%, afr)

Conditions

Inborn genetic diseases

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 -7.2	GERP -4.4
Overall
CADD	1.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.641% African / African-American · 364/56,789 alleles

Filtering AF 0.587% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.565%

Overall 0.0413% 498/1,206,996 alleles · rare exomes 276/1,096,628 · genomes 222/110,368 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.641%	156
Remaining individualsnot grpmax-eligible	0.0736%	1,358
Admixed American	0.0725%	1,380
Middle Eastern	0.0231%	4,332
European (non-Finnish)	0.00705%	14,188
East Asian	0.00298%	33,602
South Asian	0.00177%	56,385

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FGD1
Protein: p.Pro539=
Coding: c.1617G>A
MANE Select: NM_004463
dbSNP: rs151184308
Type: single nucleotide variant
Location: chrX:54465470 (GRCh38)
Structure: AlphaFold pLDDT 66.18
Residue 539: the dh domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGD1 p.Arg519Cys Likely pathogenic ★★ same condition
FGD1 p.Arg153Trp Uncertain significance ★★ same condition
FGD1 p.Arg281Gln Uncertain significance ★★ ⚠ same condition
FGD1 p.Arg522Ser Uncertain significance ★★ ⚠ same condition
FGD1 p.Arg723Trp Uncertain significance ★★ ⚠ same condition
FGD1 p.Asp191Asn Uncertain significance ★★ ⚠ same condition
FGD1 p.Glu812= Uncertain significance ★★ same condition
FGD1 p.Glu953Lys 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-pro539 (accessed [today's date]).

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