Is PGBD3 p.Val375Met (c.1123G>A) pathogenic?

PGBD3 p.Val375Met (c.1123G>A) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.2275); Ultra-rare (popmax 0.0124%, nfe).

How common is PGBD3 p.Val375Met (c.1123G>A) in the general population?

PGBD3 p.Val375Met (c.1123G>A) is ultra-rare (popmax 0.0124%, nfe) (gnomAD).

What do computational predictors say about PGBD3 p.Val375Met (c.1123G>A)?

AlphaMissense predicts likely benign (score 0.2275) — an in-silico prediction, not a clinical call.

PGBD3 p.Val375Met

c.1123G>A · rs766553083 · VCV2371315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2275 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, nfe)

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	0.2275	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.39	GERP -1.9
Overall
CADD	14.64	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 0.0124% European (non-Finnish) · 146/1,180,042 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.00929% 150/1,614,070 alleles · ultra-rare exomes 142/1,461,866 · genomes 8/152,204 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0124%	8,083
African / African-American	0.004%	24,972
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Val375Met
Coding: c.1123G>A
dbSNP: rs766553083
Type: single nucleotide variant
Location: chr10:49515992 (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-val375met (accessed [today's date]).

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