Is PLCE1 p.Asn58= (c.174C>T) pathogenic?

PLCE1 p.Asn58= (c.174C>T) is classified Conflicting classifications of pathogenicity in PLCE1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-13). Ultra-rare (popmax 0.0164%, mid); Associated with nephrotic syndrome, type 3.

What condition is associated with PLCE1 p.Asn58= (c.174C>T)?

PLCE1 p.Asn58= (c.174C>T) is associated with nephrotic syndrome, type 3 (ClinVar).

How common is PLCE1 p.Asn58= (c.174C>T) in the general population?

PLCE1 p.Asn58= (c.174C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PLCE1 p.Asn58=

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.174C>T · rs761575973 · VCV878674

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 0.42	GERP 1.3, phastCons 0.013
Overall
CADD	2.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.00508% 82/1,613,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
South Asian	0.00988%	10,120
European (non-Finnish)	0.00576%	17,350
Remaining individualsnot grpmax-eligible	0.0048%	20,821
Admixed American	0.00167%	59,946

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.Asn58=
Coding: c.174C>T
MANE Select: NM_016341
dbSNP: rs761575973
Type: single nucleotide variant
Location: chr10:94031220 (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 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
PLCE1 p.Gln1020Ter 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-asn58 (accessed [today's date]).

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