Is PLCE1 p.Asp309= (c.927T>C) pathogenic?

PLCE1 p.Asp309= (c.927T>C) is classified Uncertain significance in PLCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00334%, amr); Associated with nephrotic syndrome, type 3.

What condition is associated with PLCE1 p.Asp309= (c.927T>C)?

PLCE1 p.Asp309= (c.927T>C) is associated with nephrotic syndrome, type 3 (ClinVar).

How common is PLCE1 p.Asp309= (c.927T>C) in the general population?

PLCE1 p.Asp309= (c.927T>C) is very rare (popmax 0.00334%, amr) (gnomAD).

PLCE1 p.Asp309=

Q: How is Hereditary steroid-resistant nephrotic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.927T>C · rs764907675 · VCV880457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

nephrotic syndrome, type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -2.6
Overall
CADD	4.636	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,950 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00192% 31/1,613,694 alleles · very rare exomes 30/1,461,550 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,975
South Asian	0.00329%	30,359
European (non-Finnish)	0.0022%	45,377

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: PLCE1
Protein: p.Asp309=
Coding: c.927T>C
MANE Select: NM_016341
dbSNP: rs764907675
Type: single nucleotide variant
Location: chr10:94031973 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.01 · 3 PDB

Full PLCE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephrotic syndrome, type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary steroid-resistant nephrotic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal

Similar variants

PLCE1 p.Asp309Gly Uncertain significance ★★ ⚠ same residue
PLCE1 c.4506+1G>A Likely pathogenic ★★ same condition
PLCE1 c.6132+1G>A Likely pathogenic ★★ same condition
PLCE1 p.Arg1246Ter Pathogenic ★★ same condition
PLCE1 p.Arg1434Gln Likely pathogenic ★★ same condition
PLCE1 p.Arg1495Ter Pathogenic/Likely pathogenic ★★ same condition
PLCE1 p.Arg321Ter Pathogenic ★★ same condition
PLCE1 p.Arg493Ter Pathogenic ★★ 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/plce1-p-asp309 (accessed [today's date]).

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