Is PGBD3 p.Leu487Phe (c.1459C>T) pathogenic?

PGBD3 p.Leu487Phe (c.1459C>T) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: ambiguous (0.4186); Very rare (popmax 6.2e-05%).

How common is PGBD3 p.Leu487Phe (c.1459C>T) in the general population?

PGBD3 p.Leu487Phe (c.1459C>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about PGBD3 p.Leu487Phe (c.1459C>T)?

AlphaMissense predicts ambiguous (score 0.4186) — an in-silico prediction, not a clinical call.

PGBD3 p.Leu487Phe

c.1459C>T · VCV4567143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4186 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.4186	ambiguous
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.28	GERP -0.25
Overall
CADD	16.27	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

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,086 alleles · very rare exomes 1/1,461,792 · genomes 0/152,294 · joint denominator

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: PGBD3
Protein: p.Leu487Phe
Coding: c.1459C>T
Type: single nucleotide variant
Location: chr10:49515656 (GRCh38)

Full PGBD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/pgbd3-p-leu487phe (accessed [today's date]).

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