Is PGBD3 p.Arg478His (c.1433G>A) pathogenic?

PGBD3 p.Arg478His (c.1433G>A) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: ambiguous (0.5165); Very rare (popmax 0.00333%, amr).

How common is PGBD3 p.Arg478His (c.1433G>A) in the general population?

PGBD3 p.Arg478His (c.1433G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PGBD3 p.Arg478His (c.1433G>A)?

AlphaMissense predicts ambiguous (score 0.5165) — an in-silico prediction, not a clinical call.

PGBD3 p.Arg478His

c.1433G>A · VCV4567138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5165 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5165	ambiguous
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.93	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.78	GERP -1.9
Overall
CADD	15.22	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 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00186% 30/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
European (non-Finnish)	0.00229%	43,704
South Asian	0.0011%	91,086

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.Arg478His
Coding: c.1433G>A
MANE Select: NM_000124 · reported on NM_170753
Type: single nucleotide variant
Location: chr10:49515682 (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-arg478his (accessed [today's date]).

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