Is FGD1 p.Pro358Ser (c.1072C>T) pathogenic?

FGD1 p.Pro358Ser (c.1072C>T) is classified Uncertain significance in FGD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely benign (0.0835); Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FGD1 p.Pro358Ser (c.1072C>T)?

FGD1 p.Pro358Ser (c.1072C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FGD1 p.Pro358Ser (c.1072C>T) in the general population?

FGD1 p.Pro358Ser (c.1072C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about FGD1 p.Pro358Ser (c.1072C>T)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

FGD1 p.Pro358Ser

c.1072C>T · rs2522714580 · VCV2614313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.3	GERP -0.53, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.1 · regional, not allelic
Overall
CADD	14.39	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/894,921 alleles

Overall 8.26e-05% 1/1,210,584 alleles · very rare exomes 1/1,097,374 · genomes 0/113,210 · joint denominator

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.Pro358Ser
Coding: c.1072C>T
MANE Select: NM_004463
dbSNP: rs2522714580
Type: single nucleotide variant
Location: chrX:54470045 (GRCh38)
Structure: AlphaFold pLDDT 66.18

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.Pro358Thr Uncertain significance ★ ⚠ same residue
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

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-pro358ser (accessed [today's date]).

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