Is PLCE1 p.Val708= (c.2124G>A) pathogenic?

PLCE1 p.Val708= (c.2124G>A) is classified Benign/Likely benign in PLCE1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-07). Low-frequency (popmax 1.29%, nfe); Associated with kidney disorder.

What condition is associated with PLCE1 p.Val708= (c.2124G>A)?

PLCE1 p.Val708= (c.2124G>A) is associated with kidney disorder, nephrotic syndrome, type 3 (ClinVar).

How common is PLCE1 p.Val708= (c.2124G>A) in the general population?

PLCE1 p.Val708= (c.2124G>A) is low-frequency (popmax 1.29%, nfe) (gnomAD).

PLCE1 p.Val708=

c.2124G>A · rs61751496 · VCV260715

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.29%, nfe)

Conditions

kidney 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 2.1	GERP -2.2, phastCons 1
Overall
CADD	7.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.29% European (non-Finnish) · 15,179/1,179,952 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.26%

Overall 1.17% 18,943/1,614,092 alleles · low-frequency exomes 17,519/1,461,808 · genomes 1,424/152,284 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.96%	25
European (non-Finnish)grpmax	1.29%	78
Amishnot grpmax-eligible	0.987%	101
Remaining individualsnot grpmax-eligible	0.942%	106
South Asian	0.346%	289
Ashkenazi Jewishnot grpmax-eligible	0.247%	406
African / African-American	0.188%	532
Admixed American	0.157%	639
Middle Eastern	0.115%	866

Finnish 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.Val708=
Coding: c.2124G>A
MANE Select: NM_016341
dbSNP: rs61751496
Type: single nucleotide variant
Location: chr10:94234222 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.01 · 3 PDB
Residue 708: the ras-gef domain

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

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephrotic syndrome, type 3

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-val708 (accessed [today's date]).

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