Is PLCE1 p.Arg688Ser (c.2064A>C) pathogenic?

PLCE1 p.Arg688Ser (c.2064A>C) is classified Uncertain significance in PLCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.5821); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PLCE1 p.Arg688Ser (c.2064A>C)?

PLCE1 p.Arg688Ser (c.2064A>C) is associated with Inborn genetic diseases (ClinVar).

How common is PLCE1 p.Arg688Ser (c.2064A>C) in the general population?

PLCE1 p.Arg688Ser (c.2064A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCE1 p.Arg688Ser (c.2064A>C)?

AlphaMissense predicts likely pathogenic (score 0.5821) — an in-silico prediction, not a clinical call.

PLCE1 p.Arg688Ser

c.2064A>C · VCV3933753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5821 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5821	likely pathogenic
REVEL	0.19	benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.78, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 214 kb · p 0.44 · regional, not allelic
Overall
CADD	20.9	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.Arg688Ser
Coding: c.2064A>C
MANE Select: NM_016341
Type: single nucleotide variant
Location: chr10:94234162 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.01 · 3 PDB
Residue 688: the ras-gef domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLCE1 c.4917+3G>A Uncertain significance ★★ same condition
PLCE1 p.Arg1057Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg1116Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg1118Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg1147Gly Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg693Cys Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg729Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg775Trp 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-arg688ser (accessed [today's date]).

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