Is PLCD1 p.Met495fs (c.1483del) pathogenic?

PLCD1 p.Met495fs (c.1483del) is classified Likely pathogenic in PLCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-09). Ultra-rare (popmax 0.0117%, amr); Associated with PLCD1-related disorder.

What condition is associated with PLCD1 p.Met495fs (c.1483del)?

PLCD1 p.Met495fs (c.1483del) is associated with PLCD1-related disorder (ClinVar).

How common is PLCD1 p.Met495fs (c.1483del) in the general population?

PLCD1 p.Met495fs (c.1483del) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

PLCD1 p.Met495fs

c.1483del · rs760879574 · VCV2635865

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

PLCD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,000 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00062% 10/1,614,026 alleles · ultra-rare exomes 8/1,461,872 · genomes 2/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
African / African-American	0.00134%	74,892
European (non-Finnish)	0.000169%	590,009

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: PLCD1
Protein: p.Met495fs
Coding: c.1483del
MANE Select: NM_006225
dbSNP: rs760879574
Type: Deletion
Location: chr3:38009395 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31
Residue 495: the pi-plc y-box domain

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

Disease context

PLCD1-related disorder

Similar variants

PLCD1 p.Ile386fs Likely pathogenic same condition
PLCD1 p.Ala553Thr Conflicting classifications of pathogenicity ⚠ same condition
PLCD1 p.Glu462Lys Uncertain significance ⚠ same condition
PLCD1 c.429-5C>T Likely benign same condition
PLCD1 c.993-4G>A Likely benign same condition
PLCD1 c.993-5C>T Likely benign same condition
PLCD1 p.Ala249= Likely benign same condition
PLCD1 p.His546= Likely benign 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/plcd1-p-met495fs (accessed [today's date]).

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