Is PGBD3 p.His429Arg (c.1286A>G) pathogenic?

PGBD3 p.His429Arg (c.1286A>G) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). AlphaMissense: likely benign (0.1263); Ultra-rare (popmax 0.045%, amr).

How common is PGBD3 p.His429Arg (c.1286A>G) in the general population?

PGBD3 p.His429Arg (c.1286A>G) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about PGBD3 p.His429Arg (c.1286A>G)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

PGBD3 p.His429Arg

c.1286A>G · VCV4135245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.1263	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 0.96, phastCons 0.005
Overall
CADD	14.42	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.045% Admixed American · 27/59,998 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00217% 35/1,614,088 alleles · ultra-rare exomes 33/1,461,872 · genomes 2/152,216 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,222
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.000508%	196,672

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.His429Arg
Coding: c.1286A>G
Type: single nucleotide variant
Location: chr10:49515829 (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-his429arg (accessed [today's date]).

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