Is PGBD3 p.Leu146= (c.438T>C) pathogenic?

PGBD3 p.Leu146= (c.438T>C) is classified Likely benign in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-24). Ultra-rare (popmax 0.024%, afr).

How common is PGBD3 p.Leu146= (c.438T>C) in the general population?

PGBD3 p.Leu146= (c.438T>C) is ultra-rare (popmax 0.024%, afr) (gnomAD).

PGBD3 p.Leu146=

c.438T>C · rs200914470 · VCV765824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.48	GERP -0.083, phastCons 0.01
Overall
CADD	15.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/75,074 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00186% 30/1,614,228 alleles · ultra-rare exomes 17/1,461,878 · genomes 13/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,171
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,503
European (non-Finnish)	0.000254%	393,345

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.Leu146=
Coding: c.438T>C
dbSNP: rs200914470
Type: single nucleotide variant
Location: chr10:49516677 (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-leu146 (accessed [today's date]).

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