Is PLCE1 p.Val550Phe (c.1648G>T) pathogenic?

PLCE1 p.Val550Phe (c.1648G>T) is classified Uncertain significance in PLCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-11). AlphaMissense: likely pathogenic (0.7492); Absent from gnomAD v4.1; Associated with nephrotic syndrome, type 3.

What condition is associated with PLCE1 p.Val550Phe (c.1648G>T)?

PLCE1 p.Val550Phe (c.1648G>T) is associated with nephrotic syndrome, type 3 (ClinVar).

How common is PLCE1 p.Val550Phe (c.1648G>T) in the general population?

PLCE1 p.Val550Phe (c.1648G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCE1 p.Val550Phe (c.1648G>T)?

AlphaMissense predicts likely pathogenic (score 0.7492) — an in-silico prediction, not a clinical call.

PLCE1 p.Val550Phe

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.1648G>T · rs377400616 · VCV1029438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7492 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

nephrotic syndrome, type 3

Computational evidence

Protein change
AlphaMissense	0.7492	likely pathogenic
REVEL	0.48	indeterminate
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 214 kb · p 0.44 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLCE1
Protein: p.Val550Phe
Coding: c.1648G>T
MANE Select: NM_016341
dbSNP: rs377400616
Type: single nucleotide variant
Location: chr10:94171335 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.01 · 3 PDB
Residue 550: the ras-gef domain

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-val550phe (accessed [today's date]).

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