Is PLCE1 p.Asp211= (c.633C>T) pathogenic?

PLCE1 p.Asp211= (c.633C>T) is classified Conflicting classifications of pathogenicity in PLCE1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-13). Rare (popmax 0.147%, afr); Associated with nephrotic syndrome, type 3.

What condition is associated with PLCE1 p.Asp211= (c.633C>T)?

PLCE1 p.Asp211= (c.633C>T) is associated with nephrotic syndrome, type 3 (ClinVar).

How common is PLCE1 p.Asp211= (c.633C>T) in the general population?

PLCE1 p.Asp211= (c.633C>T) is rare (popmax 0.147%, afr) (gnomAD).

PLCE1 p.Asp211=

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.633C>T · rs201117145 · VCV301686

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.147%, afr)

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 0.31	GERP -2.8, phastCons 1
Overall
CADD	7.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% African / African-American · 110/74,984 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0113% 183/1,613,694 alleles · rare exomes 112/1,461,540 · genomes 71/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.147%	682
Middle Eastern	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0352%	2,840
East Asian	0.0245%	4,078
Admixed American	0.0183%	5,451
South Asian	0.00549%	18,214
European (non-Finnish)	0.00178%	56,181

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.Asp211=
Coding: c.633C>T
MANE Select: NM_016341
dbSNP: rs201117145
Type: single nucleotide variant
Location: chr10:94031679 (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-asp211 (accessed [today's date]).

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