Is PGBD3 p.Arg199Cys (c.595C>T) pathogenic?

PGBD3 p.Arg199Cys (c.595C>T) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.6373); Very rare (popmax 0.00667%, amr).

How common is PGBD3 p.Arg199Cys (c.595C>T) in the general population?

PGBD3 p.Arg199Cys (c.595C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about PGBD3 p.Arg199Cys (c.595C>T)?

AlphaMissense predicts likely pathogenic (score 0.6373) — an in-silico prediction, not a clinical call.

PGBD3 p.Arg199Cys

c.595C>T · VCV4135252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6373 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/3 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	0.6373	likely pathogenic
REVEL	0.065	moderately benign-leaning
SaProt	LLR -11.44	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.4	GERP -2.2
Overall
CADD	15.33	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 0.00667% Admixed American · 4/59,990 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00062% 10/1,613,926 alleles · very rare exomes 4/1,461,838 · genomes 6/152,088 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
African / African-American	0.00401%	24,959
Remaining individualsnot grpmax-eligible	0.0032%	31,242
South Asian	0.0011%	91,050

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.Arg199Cys
Coding: c.595C>T
Type: single nucleotide variant
Location: chr10:49516520 (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-arg199cys (accessed [today's date]).

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