Is FGD1 p.Pro712= (c.2136A>G) pathogenic?

FGD1 p.Pro712= (c.2136A>G) is classified Benign in FGD1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 42.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with FGD1 p.Pro712= (c.2136A>G)?

FGD1 p.Pro712= (c.2136A>G) is associated with Inborn genetic diseases (ClinVar).

FGD1 p.Pro712=

Q: How common is FGD1 p.Pro712= (c.2136A>G) in the general population?

FGD1 p.Pro712= (c.2136A>G) is common (popmax 42.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2136A>G · rs1126744 · VCV95089

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 42.8%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.047	GERP -4.2, phastCons 0.24
Overall
CADD	1.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.8% African / African-American · 23,809/55,665 alleles

Filtering AF 42.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.1%

Overall 4.54% 54,098/1,190,574 alleles · common exomes 38,667/1,080,756 · genomes 15,431/109,818 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	42.8%	2
South Asian	9.54%	10
East Asian	8.96%	11
Remaining individualsnot grpmax-eligible	6.61%	15
Middle Eastern	5.98%	17
Admixed American	4.64%	22
Finnishnot grpmax-eligible	2.74%	36
Ashkenazi Jewishnot grpmax-eligible	1.8%	56
European (non-Finnish)	1.68%	59
Amishnot grpmax-eligible	0.59%	169

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.Pro712=
Coding: c.2136A>G
MANE Select: NM_004463
dbSNP: rs1126744
Type: single nucleotide variant
Location: chrX:54449671 (GRCh38)
Structure: AlphaFold pLDDT 66.18
Residue 712: the 'disordered' region

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-pro712 (accessed [today's date]).

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