Is PGBD3 p.Arg474Trp (c.1420C>T) pathogenic?

PGBD3 p.Arg474Trp (c.1420C>T) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: ambiguous (0.3583); Ultra-rare (popmax 0.0286%, sas).

How common is PGBD3 p.Arg474Trp (c.1420C>T) in the general population?

PGBD3 p.Arg474Trp (c.1420C>T) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

What do computational predictors say about PGBD3 p.Arg474Trp (c.1420C>T)?

AlphaMissense predicts ambiguous (score 0.3583) — an in-silico prediction, not a clinical call.

PGBD3 p.Arg474Trp

c.1420C>T · VCV3305966

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3583	ambiguous
REVEL	0.056	moderately benign-leaning
SaProt	LLR -12.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.23	GERP -1.9, phastCons 0.001
Overall
CADD	15.24	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 0.0286% South Asian · 26/91,062 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0039% 63/1,614,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0286%	3,502
Admixed American	0.025%	4,001
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.00153%	65,556
African / African-American	0.00133%	75,012

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.Arg474Trp
Coding: c.1420C>T
MANE Select: NM_000124 · reported on NM_170753
Type: single nucleotide variant
Location: chr10:49515695 (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-arg474trp (accessed [today's date]).

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