Is PLCD1 p.Phe236Leu (c.706T>C) pathogenic?

PLCD1 p.Phe236Leu (c.706T>C) is classified Uncertain significance in PLCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely pathogenic (0.9882); Absent from gnomAD v4.1.

How common is PLCD1 p.Phe236Leu (c.706T>C) in the general population?

PLCD1 p.Phe236Leu (c.706T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLCD1 p.Phe236Leu (c.706T>C)?

AlphaMissense predicts likely pathogenic (score 0.9882) — an in-silico prediction, not a clinical call.

PLCD1 p.Phe236Leu

c.706T>C · rs2470979209 · VCV3214432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9882 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9882	likely pathogenic · top 5% in PLCD1
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -12.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Phe236Leu
Coding: c.706T>C
MANE Select: NM_006225
dbSNP: rs2470979209
Type: single nucleotide variant
Location: chr3:38011298 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31

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-phe236leu (accessed [today's date]).

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