Is PLCE1 p.Pro1705= (c.5115G>A) pathogenic?

PLCE1 p.Pro1705= (c.5115G>A) is classified Conflicting classifications of pathogenicity in PLCE1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-04). Very rare (popmax 0.00585%, nfe); Associated with PLCE1-related disorder.

What condition is associated with PLCE1 p.Pro1705= (c.5115G>A)?

PLCE1 p.Pro1705= (c.5115G>A) is associated with PLCE1-related disorder (ClinVar).

How common is PLCE1 p.Pro1705= (c.5115G>A) in the general population?

PLCE1 p.Pro1705= (c.5115G>A) is very rare (popmax 0.00585%, nfe) (gnomAD).

PLCE1 p.Pro1705=

c.5115G>A · rs751378446 · VCV2634683

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Conditions

PLCE1-related disorder

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 1.1	GERP -2.2, phastCons 1
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00585% European (non-Finnish) · 69/1,179,850 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00688% 111/1,613,728 alleles · very rare exomes 100/1,461,598 · genomes 11/152,130 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,345
Remaining individualsnot grpmax-eligible	0.0192%	5,206
European (non-Finnish)grpmax	0.00585%	17,099
East Asian	0.00446%	22,437
Admixed American	0.00333%	29,992
South Asian	0.00329%	30,358
African / African-American	0.00134%	74,884

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1705=
Coding: c.5115G>A
MANE Select: NM_016341
dbSNP: rs751378446
Type: single nucleotide variant
Location: chr10:94293587 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.01 · 3 PDB
Residue 1705: the 'required for activation by rhoa, rhob, gna12, gna13 and g-beta gamma' region; a UniProt-annotated variant site (in nphs3); the 'disordered' region

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

Disease context

PLCE1-related disorder

Similar variants

PLCE1 p.Arg321Ter Pathogenic ★★ same condition
PLCE1 p.Arg493Ter Pathogenic ★★ same condition
PLCE1 p.Gln1020Ter Pathogenic ★★ same condition
PLCE1 p.His987Arg Uncertain significance ★★ ⚠ same condition
PLCE1 p.Leu1552Ter Likely pathogenic ★ same condition
PLCE1 p.Gly1194Arg Uncertain significance ★ ⚠ same condition
PLCE1 p.Pro1678Thr Uncertain significance ★ ⚠ same condition
PLCE1 c.1207-43013G>T 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/plce1-p-pro1705 (accessed [today's date]).

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