Is PLCD1 p.Ile201Ser (c.602T>G) pathogenic?

PLCD1 p.Ile201Ser (c.602T>G) is classified Uncertain significance in PLCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.8877); Absent from gnomAD v4.1.

How common is PLCD1 p.Ile201Ser (c.602T>G) in the general population?

PLCD1 p.Ile201Ser (c.602T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCD1 p.Ile201Ser (c.602T>G)?

AlphaMissense predicts likely pathogenic (score 0.8877) — an in-silico prediction, not a clinical call.

PLCD1 p.Ile201Ser

c.602T>G · VCV4568921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8877	likely pathogenic
REVEL	0.662	pathogenic-leaning
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	28.0	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: PLCD1
Protein: p.Ile201Ser
Coding: c.602T>G
MANE Select: NM_006225
Type: single nucleotide variant
Location: chr3:38011402 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31
Residue 201: the ef-hand 2 domain

Full PLCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLCD1 p.Arg530Ter Pathogenic/Likely pathogenic ★★ same type
PLCD1 p.Arg138His Uncertain significance ★★ ⚠ same type
PLCD1 p.Arg476His Uncertain significance ★★ ⚠ same type
PLCD1 p.Arg60Gln Uncertain significance ★★ ⚠ same type
PLCD1 p.Pro417Arg Uncertain significance ★★ ⚠ same type
PLCD1 p.Ser650Ala Uncertain significance ★★ ⚠ same type
PLCD1 c.1607-42C>T Benign ★★ same type
PLCD1 c.1724-186C>G Benign ★★ same type

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/plcd1-p-ile201ser (accessed [today's date]).

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